Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 394, Issue 7

Issues

Targeting caspases in cancer therapeutics

Patrick Hensley
  • Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA
  • Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Murli Mishra
  • Graduate Center for Toxicology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Natasha Kyprianou
  • Corresponding author
  • Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA
  • Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA
  • Graduate Center for Toxicology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-03-18 | DOI: https://doi.org/10.1515/hsz-2013-0128

Abstract

The identification of the fundamental role of apoptosis in the growth balance and normal homeostasis against cell proliferation led to the recognition of its loss contributing to tumorigenesis. The mechanistic significance of reinstating apoptosis signaling towards selective targeting of malignant cells heavily exploits the caspase family of death-inducing molecules as a powerful therapeutic platform for the development of potent anticancer strategies. Some apoptosis inhibitors induce caspase expression and activity in preclinical models and clinical trials by targeting both the intrinsic and extrinsic apoptotic pathways and restoring the apoptotic capacity in human tumors. Furthermore, up-regulation of caspases emerges as a sensitizing mechanism for tumors exhibiting therapeutic resistance to radiation and adjuvant chemotherapy. This review provides a comprehensive discussion of the functional involvement of caspases in apoptosis control and the current understanding of reactivating caspase-mediated apoptosis signaling towards effective therapeutic modalities in cancer treatment.

Keywords: apoptin; apoptosis, caspase; prostate cancer; quinazolines; survivin

References

  • Adida, C., Crotty, P.L., McGrath, J., Berrebi, D., Diebold, J., and Altieri, D.C. (1998). Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am. J. Pathol. 152, 43–49.Google Scholar

  • Aggarwal, S., Kim, S.W., Cheon, K., Tabassam, F.H., Yoon, J.H., and Koo, J.S. (2006). Nonclassical action of retinoic acid on the activation of the cAMP response element-binding protein in normal human bronchial epithelial cells. Mol. Biol. Cell. 17, 566–575.CrossrefPubMedGoogle Scholar

  • Alnemri, E., Livingston, D., Nicholson, D., Salvesen, G., Thornberry, N., Wong, W., and Yuan, J. (1996). Human ICE/CED-3 Protease Nomenclature. Cell 87, 171.CrossrefPubMedGoogle Scholar

  • Altieri, D.C. (2008). Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer 8, 61–70.CrossrefPubMedGoogle Scholar

  • Altieri, D.C. (2006). The case for survivin as a regulator of microtubule dynamics and cell-death decisions. Curr. Opin. Cell. Biol. 18, 609–615.CrossrefPubMedGoogle Scholar

  • Andersen, M.H., Soerensen, R.B., Becker, J.C., and Thor Straten, P. (2006). HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer. J. Transl. Med. 4, 38.CrossrefGoogle Scholar

  • Aoki, Y., Feldman, G.M., and Tosato, G. (2003). Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 101, 1535–1542.CrossrefGoogle Scholar

  • Backendorf, C., Visser, A.E., de Boer, A.G., Zimmerman, R., Visser, M., Voskamp, P., Zhang, Y.H., and Noteborn, M. (2008). Apoptin: therapeutic potential of an early sensor of carcinogenic transformation. Annu. Rev. Pharmacol. Toxicol. 48, 143–169.PubMedCrossrefGoogle Scholar

  • Banelli, B., Casciano, I., Croce, M., Di Vinci, A., Gelvi, I., Pagnan, G., Brignole, C., Allemanni, G., Ferrini, S., Ponzoni, M., and Romani, M. (2002). Expression and methylation of CASP8 in neuroblastoma: identification of a promoter region. Nat. Med. 8, 1333–1335.Google Scholar

  • Banks, D.P., Plescia, J., Altieri, D.C., Chen, J., Rosenberg, S.H., Zhang, H., and Ng, S.C. (2000). Survivin does not inhibit caspase-3 activity. Blood 96, 4002–4003.PubMedGoogle Scholar

  • Beltinger, C., Fulda, S., Kammertoens, T., Meyer, E., Uckert, W., and Debatin, K.M. (1999). Herpes simplex virus thymidine kinase/ganciclovir-induced apoptosis involves ligand-independent death receptor aggregation and activation of caspases. Proc. Natl. Acad. Sci. USA 96, 8699–8704.CrossrefGoogle Scholar

  • Benning, C.M. and Kyprianou, N. (2002). Quinazoline-derived alpha1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an alpha1-adrenoceptor-independent action. Cancer Res. 62, 597–602.PubMedGoogle Scholar

  • Burek, M., Maddika, S., Burek, C.J., Daniel, P.T., Schulze-Osthoff, K., and Los, M. (2006). Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1 dependent. Oncogene. 25, 2213–2222.CrossrefPubMedGoogle Scholar

  • Carrasco, R.A., Stamm, N.B., Marcusson, E., Sandusky, G., Iversen, P., and Patel, B.K. (2011). Antisense inhibition of survivin expression as a cancer therapeutic. Mol. Cancer Ther. 10, 221–232.CrossrefPubMedGoogle Scholar

  • Cancer Genome Atlas Network (2012). Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70.Google Scholar

  • Casciano, I., De Ambrosis, A., Croce, M., Pagnan, G., Di Vinci, A., Allemanni, G., Banelli, B., Ponzoni, M., Romani, M., and Ferrini, S. (2004). Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE). Cell Death Differ. 11, 131–134.PubMedGoogle Scholar

  • Chang, C.C., Heller, J.D., Kuo, J., and Huang, R.C. (2004). Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression. Proc. Natl. Acad. Sci. USA 101, 13239–13244.CrossrefGoogle Scholar

  • Church, D.N. and Talbot, D.C. (2012). Survivin in solid tumors: rationale for development of inhibitors. Curr. Oncol. Rep. 14, 120–128.PubMedCrossrefGoogle Scholar

  • Clackson, T., Yang, W., Rozamus, L.W., Hatada, M., Amara, J.F., Rollins, C.T., Stevenson, L.F., Magari, S.R., Wood, S.A., Courage, N.L., et al. (1998). Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc. Natl. Acad. Sci. USA 95, 10437–10442.CrossrefGoogle Scholar

  • Danen-Van Oorschot, A.A., Fischer, D.F., Grimbergen, J.M., Klein, B., Zhuang, S., Falkenburg, J.H., Backendorf, C., Quax, P.H., Van der, E.b A.J., and Noteborn, M.H. (1997). Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells. Proc. Natl. Acad. Sci. USA 94, 5843–5847.CrossrefGoogle Scholar

  • Danen-Van Oorschot, A.A., Zhang, Y.H., Leliveld, S.R., Rohn, J.L., Seelen, M.C., Bolk, M.W., Van Zon, A., Erkeland, S.J., Abrahams, J.P., Mumberg, D., et al. (2003). Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis. J. Biol. Chem. 278, 27729–27736.CrossrefGoogle Scholar

  • Darnell, J.E. Jr., Kerr, I.M., and Stark, G.R. (1994). Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415–1421.Google Scholar

  • Eggert, A., Grotzer, M.A., Zuzak, T.J., Wiewrodt, B.R., Ho, R., Ikegaki, N., and Brodeur, G.M. (2001). Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. Cancer Res. 61, 1314–1319.PubMedGoogle Scholar

  • Ehrlich, M. (2009). DNA hypomethylation in cancer cells. Epigenomics 1, 239–259.CrossrefPubMedGoogle Scholar

  • Favaloro, B., Allocati, N., Graziano, V., Di Ilio, C., and De Laurenzi, V. (2012). Role of apoptosis in disease. Aging (Albany NY) 4, 330–349.Google Scholar

  • Fenaux, P., Mufti, G.J., Hellstrom-Lindberg, E., Santini, V., Finelli, C., Giagounidis, A., Schoch, R., Gattermann, N., Sanz, G., List, A., et al. International Vidaza High-Risk MDS Survival Study Group. (2009). Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 10, 223–232.CrossrefGoogle Scholar

  • Fiandalo, M.V. and Kyprianou, N. (2012). Caspase control: protagonists of cancer cell apoptosis. Exp. Oncol. 34, 165–175.PubMedGoogle Scholar

  • Fuchs, Y. and Steller, H. (2011). Programmed cell death in animal development and disease. Cell 147, 742–758.PubMedCrossrefGoogle Scholar

  • Fuentes-Prior, P. and Salvesen, G.S. (2004). The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J. 384, 201–232.Google Scholar

  • Fukamiya, N. and Lee, K.H. (1986). Antitumor agents, 81. Justicidin-A and diphyllin, two cytotoxic principles from Justicia procumbens. J. Nat. Prod. 49, 348–350.CrossrefGoogle Scholar

  • Fulciniti, M., Amin, S., Nanjappa, P., Rodig, S., Prabhala, R., Li, C., Minvielle, S., Tai, Y.T., Tassone, P., Avet-Loiseau, H., Hideshima, T., et al. (2011). Significant biological role of sp1 transactivation in multiple myeloma. Clin. Cancer Res. 17, 6500–6509.CrossrefGoogle Scholar

  • Fulda, S. and Debatin, K.M. (2006). 5-Aza-2′-deoxycytidine and IFN-gamma cooperate to sensitize for TRAIL-induced apoptosis by upregulating caspase-8. Oncogene. 25, 5125–5133.Google Scholar

  • Fulda, S. and Debatin, K.M. (2002). IFNγ sensitizes for apoptosis by upregulating caspase-8 expression through the Stat1 pathway. Oncogene 21, 2295–2308.Google Scholar

  • Fulda, S., Küfer, M.U., Meyer, E., van Valen, F., Dockhorn-Dworniczak, B., and Debatin, K.M. (2001). Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 20, 5865–5877.PubMedGoogle Scholar

  • Garrison, J.B., Shaw, Y.J., Chen, C.S., and Kyprianou, N. (2007). Novel quinazoline-based compounds impair prostate tumorigenesis by targeting tumor vascularity. Cancer Res. 67, 11344–11352.CrossrefPubMedGoogle Scholar

  • Geiger, K., Hagenbuchner, J., Rupp, M., Fiegl, H., Sergi, C., Meister, B., Kiechl-Kohlendorfer, U., Müller, T., Ausserlechner, M.J., and Obexer, P. (2012). FOXO3/FKHRL1 is activated by 5-aza-2-deoxycytidine and induces silenced caspase-8 in neuroblastoma. Mol. Biol. Cell 23, 2226–2234.Google Scholar

  • Ghobrial, I.M., Witzig, T.E., and Adjei, A.A. (2005). Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin. 55, 178–194.CrossrefGoogle Scholar

  • Giaccone, G., Zatloukal, P., Roubec, J., Floor, K., Musil, J., Kuta, M., van Klaveren, R.J., Chaudhary, S., Gunther, A., and Shamsili, S. (2009). Multicenter phase II trial of YM155, a small-molecule suppressor of survivin, in patients with advanced, refractory, non-small-cell lung cancer. J. Clin. Oncol. 27, 4481–4486.CrossrefGoogle Scholar

  • Gillies, R.J., Verduzco, D., and Gatenby, R.A. (2012). Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nat. Rev. Cancer 12, 487–493.PubMedCrossrefGoogle Scholar

  • Grotzer, M.A., Eggert, A., Zuzak, T.J., Janss, A.J., Marwaha, S., Wiewrodt, B.R., Ikegaki, N., Brodeur, G.M., and Phillips, P.C. (2000). Resistance to TRAIL-induced apoptosis in primitive neuroectodermal brain tumor cells correlates with a loss of caspase-8 expression. Oncogene 19, 4604–4610.CrossrefPubMedGoogle Scholar

  • Grossman, S.A., Ye, X., Peereboom, D., Rosenfeld, M.R., Mikkelsen, T., Supko, J.G., and Desideri, S.; Adult Brain Tumor Consortium. (2012). Phase I study of terameprocol in patients with recurrent high-grade glioma. Neuro. Oncol. 14, 511–517.PubMedCrossrefGoogle Scholar

  • Guelen, L., Paterson, H., Gäken, J., Meyers, M., Farzaneh, F., and Tavassoli, M. (2004). TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. Oncogene 23, 1153–1165.CrossrefPubMedGoogle Scholar

  • Guha, M., Plescia, J., Leav, I., Li, J., Languino, L.R., and Altieri, D.C. (2009). Endogenous tumor suppression mediated by PTEN involves survivin gene silencing. Cancer Res. 69, 4954–4958.PubMedCrossrefGoogle Scholar

  • Gyurkocza, B., Plescia, J., Raskett, C.M., Garlick, D.S., Lowry, P.A., Carter, B.Z., Andreeff, M., Meli, M., Colombo, G., and Altieri, D.C. (2006). Antileukemic activity of shepherdin and molecular diversity of hsp90 inhibitors. J. Natl. Cancer Inst. 98, 1068–1077.CrossrefGoogle Scholar

  • Hansen, J.B., Fisker, N., Westergaard, M., Kjaerulff, L.S., Hansen, H.F., Thrue, C.A., Rosenbohm, C., Wissenbach, M., Orum, H., and Koch, T. (2008). SPC3042: a proapoptotic survivin inhibitor. Mol. Cancer Ther. 7, 2736–2745.CrossrefPubMedGoogle Scholar

  • Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646–674.PubMedCrossrefGoogle Scholar

  • He, X.L., Zhang, P., Dong, X.Z., Yang, M.H., Chen, S.L., and Bi, M.G. (2012). JR6, a new compound isolated from Justicia procumbens, induces apoptosis in human bladder cancer EJ cells through caspase-dependent pathway. J. Ethnopharmacol. 144, 284–292.CrossrefGoogle Scholar

  • Hensley, P.J. and Kyprianou, N. (2012). Modeling prostate cancer in mice: limitations and opportunities. J. Androl. 33, 133–144.CrossrefGoogle Scholar

  • Hopkins-Donaldson, S., Bodmer, J.L., Bourloud, K.B., Brognara, C.B., Tschopp, J., and Gross, N. (2000). Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res. 60, 4315–4319.Google Scholar

  • Herman, J.G. and Baylin, S.B. (2003). Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349, 2042–2054.CrossrefGoogle Scholar

  • Hirohashi, Y., Torigoe, T., Maeda, A., Nabeta, Y., Kamiguchi, K., Sato, T., Yoda, J., Ikeda, H., Hirata, K., Yamanaka, N., et al. (2002). An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin. Clin. Cancer Res. 8, 1731–1739.PubMedGoogle Scholar

  • Iwasa, T., Okamoto, I., Suzuki, M., Nakahara, T., Yamanaka, K., Hatashita, E., Yamada, Y., Fukuoka, M., Ono, K., and Nakagawa, K. (2008). Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines. Clin. Cancer Res. 14, 6496–6504.CrossrefGoogle Scholar

  • Iwasa, T., Okamoto, I., Takezawa, K., Yamanaka, K., Nakahara, T., Kita, A., Koutoku, H., Sasamata, M., Hatashita, E., Yamada, Y., et al. (2010). Marked anti-tumour activity of the combination of YM155, a novel survivin suppressant, and platinum-based drugs. Br. J. Cancer 103, 36–42.Google Scholar

  • Jacob, N.K., Cooley, J.V., Shirai, K., and Chakravarti, A. (2012). Survivin splice variants are not essential for mitotic progression or inhibition of apoptosis induced by doxorubicin and radiation. Onco. Targets Ther. 5, 7–20.PubMedCrossrefGoogle Scholar

  • Jänicke, R.U. (2009). MCF-7 breast carcinoma cells do not express caspase-3. Breast Cancer Res. Treat. 117, 219–221.Google Scholar

  • Jänicke, R.U., Sprengart, M.L., Wati, M.R., and Porter, A.G. (1998). Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem. 273, 9357–9360.Google Scholar

  • Jiang, S.Y., Wu, M.S., Chen, L.M., Hung, M.W., Lin, H.E., Chang, G.G., and Chang, T.C. (2005). Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter. Biochem. Biophys. Res. Commun. 331, 630–639.Google Scholar

  • Jiang, M., Zhu, K., Grenet, J., and Lahti, J.M. (2008). Retinoic acid induces caspase-8 transcription via phospho-CREB and increases apoptotic responses to death stimuli in neuroblastoma cells. Biochim. Biophys. Acta 1783, 1055–1067.Google Scholar

  • Jiang, Y., Saavedra, H.I., Holloway, M.P., Leone, G., and Altura, R.A. (2004). Aberrant regulation of survivin by the RB/E2F family of proteins. J. Biol. Chem. 279, 40511–40520.Google Scholar

  • Kawasaki, H., Altieri, D.C., Lu, C.D., Toyoda, M., Tenjo, T., and Tanigawa, N. (1998). Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 58, 5071–5074.PubMedGoogle Scholar

  • Khanna, N., Dalby, R., Tan, M., Arnold, S., Stern, J., and Frazer, N. (2007). Phase I/II clinical safety studies of terameprocol vaginal ointment. Gynecol. Oncol. 107, 554–562.PubMedCrossrefGoogle Scholar

  • Kaminskas, E., Farrell, A.T., Wang, Y.C., Sridhara, R., and Pazdur, R. (2005). FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist 10, 176–182.CrossrefGoogle Scholar

  • Kaplan, D.H., Shankaran, V., Dighe, A.S., Stockert, E., Aguet, M., Old, L.J., and Schreiber, R.D. (1998). Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice. Proc. Natl. Acad. Sci. USA 95, 7556–7561.CrossrefGoogle Scholar

  • Keledjian, K. and Kyprianou, N. (2003). Anoikis induction by quinazoline based alpha 1-adrenoceptor antagonists in prostate cancer cells: antagonistic effect of bcl-2. J. Urol. 169, 1150–1156.Google Scholar

  • Kim, S.W., Hong, J.S., Ryu, S.H., Chung, W.C., Yoon, J.H., and Koo, J.S. (2007). Regulation of mucin gene expression by CREB via a nonclassical retinoic acid signaling pathway. Mol. Cell. Biol. 27, 6933–6947.CrossrefGoogle Scholar

  • Kita, A., Mitsuoka, K., Kaneko, N., Nakata, M., Yamanaka, K., Jitsuoka, M., Miyoshi, S., Noda, A., Mori, M., Nakahara, T., et al. (2012). Sepantronium bromide (YM155) enhances response of human B-cell non-Hodgkin lymphoma to rituximab. J. Pharmacol. Exp. Ther. 343, 178–183.Google Scholar

  • Kohno, T., Morishita, K., Takano, H., Shapiro, D.N., and Yokota, J. (1994). Homozygous deletion at chromosome 2q33 in human small-cell lung carcinoma identified by arbitrarily primed PCR genomic fingerprinting. Oncogene 9, 103–108.Google Scholar

  • Kumar, B., Yadav, A., Lang, J.C., Cipolla, M.J., Schmitt, A.C., Arradaza, N., Teknos, T.N., and Kumar, P. (2012). YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels. Mol. Cancer. Ther. 11, 1988–1998.PubMedCrossrefGoogle Scholar

  • Kyprianou, N. and Benning, C.M. (2000). Suppression of human prostate cancer cell growth by α1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis. Cancer Res. 60, 4550–4555.Google Scholar

  • Kyprianou, N., Litvak, J.P., Borkowski, A., Alexander, R., and Jacobs, S.C. (1998). Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J. Urol. 159, 1810–1815.CrossrefGoogle Scholar

  • Lepor, H. (2007). Alpha blockers for the treatment of benign prostatic hyperplasia. Rev. Urol. 9, 181–190.PubMedGoogle Scholar

  • Lladser, A., Sanhueza, C., Kiessling, R., and Quest, A.F. (2011). Is survivin the potential Achilles’ heel of cancer? Adv. Cancer. Res. 111, 1–37.PubMedCrossrefGoogle Scholar

  • Li, C., Wu, Z., Liu, M., Pazgier, M., and Lu, W. (2008). Chemically synthesized human survivin does not inhibit caspase-3. Protein Sci. 17, 1624–1629.CrossrefGoogle Scholar

  • Liedtke, C., Gröger, N., Manns, M.P., and Trautwein, C. (2006). Interferon-α enhances TRAIL-mediated apoptosis by up-regulating caspase-8 transcription in human hepatoma cells. J. Hepatol. 44, 342–249.CrossrefGoogle Scholar

  • Liedtke, C., Zschemisch, N.H., Cohrs, A., Roskams, T., Borlak, J., Manns, M.P., and Trautwein, C. (2005). Silencing of caspase-8 in murine hepatocellular carcinomas is mediated via methylation of an essential promoter element. Gastroenterology 129, 1602–1615.PubMedCrossrefGoogle Scholar

  • Liu, Y., Wei, D., Zhao, Y., Cheng, W., Lu, Y., Ma, Y., Li, X., Han, C., Wei, Y., Cao, H., et al. (2012). Synthesis and biological evaluation of a series of podophyllotoxins derivatives as a class of potent antitubulin agents. Bioorg. Med. Chem. 20, 6285–6295.CrossrefPubMedGoogle Scholar

  • Los, M., Panigrahi, S., Rashedi, I., Mandal, S., Stetefeld, J., Essmann, F., and Schulze-Osthoff, K. (2009). Apoptin, a tumor-selective killer. Biochim. Biophys. Acta 1793, 1335–1342.Google Scholar

  • Lyons, R.M. (2012). Myelodysplastic syndromes: therapy and outlook. Am. J. Med. 125, S18–S23.CrossrefGoogle Scholar

  • Maddika, S., Mendoza, F.J., Hauff, K., Zamzow, C.R., Paranjothy, T., and Los, M. (2006). Cancer-selective therapy of the future: apoptin and its mechanism of action. Cancer Biol. Ther. 5, 10–19.CrossrefPubMedGoogle Scholar

  • Martin, S.J., Henry, C.M., and Cullen, S.P. (2012). A perspective on mammalian caspases as positive and negative regulators of inflammation. Mol. Cell 46, 387–397.PubMedCrossrefGoogle Scholar

  • Masetti, R., Biagi, C., Zama, D., Vendemini, F., Martoni, A., Morello, W., Gasperini, P., and Pession, A. (2012). Retinoids in pediatric onco-hematology: the model of acute promyelocytic leukemia and neuroblastoma. Adv. Ther. 29, 747–762.PubMedCrossrefGoogle Scholar

  • Matsuo, T. and Thiele, C.J. (1998). p27Kip1: a key mediator of retinoic acid induced growth arrest in the SMS-KCNR human neuroblastoma cell line. Oncogene 16, 3337–3343.CrossrefGoogle Scholar

  • McKenzie, S. and Kyprianou, N. (2006). Apoptosis evasion: the role of survival pathways in prostate cancer progression and therapeutic resistance. J. Cell. Biochem. 97, 18–32.CrossrefGoogle Scholar

  • Mitsiades, N., Poulaki, V., Mitsiades, C., and Tsokos, M. (2001). Ewing’s sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5. Cancer Res. 61, 2704–2712.Google Scholar

  • Murakami, Y., Matsuya, T., Kita, A., Yamanaka, K., Noda, A., Mitsuoka, K., Nakahara, T., Miyoshi, S., and Nishimura, S. (2013). Radiosynthesis, biodistribution and imaging of [(11)C]YM155, a novel survivin suppressant, in a human prostate tumor-xenograft mouse model. Nucl. Med. Biol. 40, 221–226.Google Scholar

  • Muñoz-Pinedo, C. (2012). Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense. Adv. Exp. Med. Biol. 738, 124–143.Google Scholar

  • Nakahara, T., Kita, A., Yamanaka, K., Mori, M., Amino, N., Takeuchi, M., Tominaga, F., Hatakeyama, S., Kinoyama, I., Matsuhisa, A., et al. (2007). YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 67, 8014–8021.CrossrefGoogle Scholar

  • Nakahara, T., Yamanaka, K., Hatakeyama, S., Kita, A., Takeuchi, M., Kinoyama, I., Matsuhisa, A., Nakano, K., Shishido, T., Koutoku, H., et al. (2011). YM155, a novel survivin suppressant, enhances taxane-induced apoptosis and tumor regression in a human Calu 6 lung cancer xenograft model. Anticancer Drugs 22, 454–462.CrossrefGoogle Scholar

  • Natesan, S., Kataria, J.M., Dhama, K., Bhardwaj, N., and Sylvester, A. (2006). Anti-neoplastic effect of chicken anemia virus VP3 protein (apoptin) in Rous sarcoma virus-induced tumours in chicken. J. Gen. Virol. 87, 2933–2940.CrossrefGoogle Scholar

  • Negrini, S., Gorgoulis, V.G., and Halazonetis, T.D. (2012). Genomic instability – an evolving hallmark of cancer. Nat. Rev. Mol. Cell. Biol. 11, 220–228.CrossrefGoogle Scholar

  • Ocker, M. and Höpfner, M. (2012). Apoptosis-modulating drugs for improved cancer therapy. Eur. Surg. Res. 48, 111–120.PubMedCrossrefGoogle Scholar

  • Ogasawara, J., Suda, T., and Nagata, S. (1995). Selective apoptosis of CD4+CD8+ thymocytes by the anti-Fas antibody. J. Exp. Med. 181, 485–491.Google Scholar

  • Olijslagers, S.J., Zhang, Y.H., Backendorf, C., and Noteborn, M.H. (2007). Additive cytotoxic effect of apoptin and chemotherapeutic agents paclitaxel and etoposide on human tumour cells. Basic Clin. Pharmacol. Toxicol. 100, 127–131.PubMedGoogle Scholar

  • Partin, J.V., Anglin, I.E., and Kyprianou, N. (2003). Quinazoline-based alpha 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-β signalling and IκB α induction. Br. J. Cancer 88, 1615–1621.Google Scholar

  • Pietersen, A.M., van der, Eb M.M., Rademaker, H.J., van den Wollenberg, D.J., Rabelink, M.J., Kuppen, P.J., van Dierendonck, J.H., van Ormondt, H., Masman, D., van de Velde, C.J., et al. (1999). Specific tumor-cell killing with adenovirus vectors containing the apoptin gene. Gene Ther. 6, 882–892.CrossrefGoogle Scholar

  • Poon, I.K., Oro, C., Dias, M.M., Zhang, J.P., and Jans, D.A. (2005). A tumor cell-specific nuclear targeting signal within chicken anemia virus VP3/apoptin. J. Virol. 79, 1339–1341.CrossrefGoogle Scholar

  • Redfern, C.P., Lovat, P.E., Malcolm, A.J., and Pearson, A.D. (1995). Gene expression and neuroblastoma cell differentiation in response to retinoic acid: differential effects of 9-cis and all-trans retinoic acid. Eur. J. Cancer 31A, 486–494.CrossrefGoogle Scholar

  • Rennebeck, G., Martelli, M., and Kyprianou, N. (2005). Anoikis and survival connections in the tumor microenvironment: is there a role in prostate cancer metastasis? Cancer Res. 65, 11230–11235.CrossrefGoogle Scholar

  • Rohn, J.L., Zhang, Y.H., Aalbers, R.I., Otto, N., Den Hertog, J., Henriquez, N.V., Van De Velde, C.J., Kuppen, P.J., Mumberg, D., Donner, P., et al. (2002). A tumor-specific kinase activity regulates the viral death protein Apoptin. J. Biol. Chem. 277, 50820–50827.Google Scholar

  • Ruiz-Ruiz, C., Muñoz-Pinedo, C., and López-Rivas, A. (2000). Interferon-gamma treatment elevates caspase-8 expression and sensitizes human breast tumor cells to a death receptor-induced mitochondria-operated apoptotic program. Cancer Res. 60, 5673–5680.Google Scholar

  • Ruiz-Ruiz, C., Ruiz de Almodóvar, C., Rodríguez, A., Ortiz-Ferrón, G., Redondo, J.M., López-and Rivas A. (2004). The up-regulation of human caspase-8 by interferon-γ in breast tumor cells requires the induction and action of the transcription factor interferon regulatory factor-1. J. Biol. Chem. 279, 19712–19720.Google Scholar

  • Sakamoto, S. and Kyprianou, N. (2010). Targeting anoikis resistance in prostate cancer metastasis. Mol. Aspects. Med. 31, 205–214.PubMedCrossrefGoogle Scholar

  • Sakamoto, S., Schwarze, S., and Kyprianou, N. (2011). Anoikis disruption of focal adhesion-Akt signaling impairs renal cell carcinoma. Eur. Urol. 59, 734–744.CrossrefPubMedGoogle Scholar

  • Salvesen, G.S. and Duckett, C.S. (2002). IAP proteins: blocking the road to death’s door. Nat. Rev. Mol. Cell. Biol. 3, 401–410.CrossrefGoogle Scholar

  • Salvesen, G.S. and Riedl, S.J. (2008). Caspase mechanisms. Adv. Exp. Med. Biol. 615, 13–23.Google Scholar

  • Sartor, A.O. and Fitzpatrick, J.M. (2012). Urologists and oncologists: adapting to a new treatment paradigm in castration-resistant prostate cancer (CRPC). BJU Int. 110, 328–335.PubMedCrossrefGoogle Scholar

  • Satoh, T., Okamoto, I., Miyazaki, M., Morinaga, R., Tsuya, A., Hasegawa, Y., Terashima, M., Ueda, S., Fukuoka, M., Ariyoshi, Y., et al. (2009). Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors. Clin. Cancer Res. 15, 3872–3880.CrossrefGoogle Scholar

  • Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K.J., Debatin, K.M., Krammer, P.H., and Peter, M.E. (1998). Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 17, 1675–1687.CrossrefGoogle Scholar

  • Schroder, K. and Tschopp, J. (2012). The inflammasomes. Cell 140, 821–832.CrossrefGoogle Scholar

  • Shariat, S.F., Desai, S., Song, W., Khan, T., Zhao, J., Nguyen, C., Foster, B.A., Greenberg, N., Spencer, D.M., and Slawin, K.M. (2001). Adenovirus-mediated transfer of inducible caspases: a novel “death switch” gene therapeutic approach to prostate cancer. Cancer Res. 61, 2562–2571.PubMedGoogle Scholar

  • Shivapurkar, N., Toyooka, S., Eby, M.T., Huang, C.X., Sathyanarayana, U.G., Cunningham, H.T., Reddy, J.L., Brambilla, E., Takahashi, T., Minna, J.D., et al. (2002). Differential inactivation of caspase-8 in lung cancers. Cancer Biol. Ther. 1, 65–69.PubMedCrossrefGoogle Scholar

  • Shore, N., Mason, M., and de Reijke, T.M. (2012). New developments in castrate-resistant prostate cancer. BJU Int. 109, 22–32.CrossrefGoogle Scholar

  • Siegel, R., DeSantis, C., Virgo, K., Stein, K., Mariotto, A., Smith, T., Cooper, D., Gansler, T., Lerro, C., Fedewa, S., et al. (2012). Cancer treatment and survivorship statistics, 2012. CA Cancer J. Clin. 62, 220–241.Google Scholar

  • Siegelin, M.D., Plescia, J., Raskett, C.M., Gilbert, C.A., Ross, A.H., and Altieri, D.C. (2010). Global targeting of subcellular heat shock protein-90 networks for therapy of glioblastoma. Mol. Cancer Ther. 9, 1638–1646.PubMedCrossrefGoogle Scholar

  • Sonnemann, J., Hartwig, M., Plath, A., Saravana Kumar, K., Müller, C., and Beck, J.F. (2006a). Histone deacetylase inhibitors require caspase activity to induce apoptosis in lung and prostate carcinoma cells. Cancer Lett. 232, 148–160.PubMedCrossrefGoogle Scholar

  • Sonnemann, J., Kumar, K.S., Heesch, S., Müller, C., Hartwig, C., Maass, M., Bader, P., and Beck, J.F. (2006b). Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells. Int. J. Oncol. 28, 755–766.PubMedGoogle Scholar

  • Sonnemann, J., Dreyer, L., Hartwig, M., Palani, C.D., Hong le, T.T., Klier, U., Bröker, B., Völker, U., and Beck, J.F. (2007). Histone deacetylase inhibitors induce cell death and enhance the apoptosis-inducing activity of TRAIL in Ewing’s sarcoma cells. J. Cancer Res. Clin. Oncol. 133, 847–858.CrossrefGoogle Scholar

  • Storm van’s Gravesande, K., Layne, M.D., Ye, Q., Le, L., Baron, R.M., Perrella, M.A., Santambrogio, L., Silverman, E.S., and Riese, R.J. (2002). IFN regulatory factor-1 regulates IFN-γ-dependent cathepsin S expression. J. Immunol. 168, 4488–4494.Google Scholar

  • Su, C.L., Huang, L.L., Huang, L.M., Lee, J.C., Lin, C.N., and Won, S.J. (2006). Caspase-8 acts as a key upstream executor of mitochondria during justicidin A-induced apoptosis in human hepatoma cells. FEBS Lett. 580, 3185–3191.Google Scholar

  • Tamm, I., Wang, Y., Sausville, E., Scudiero, D.A., Vigna, N., Oltersdorf, T., and Reed, J.C. (1998). IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 58, 5315–5320.Google Scholar

  • Tanioka, M., Nokihara, H., Yamamoto, N., Yamada, Y., Yamada, K., Goto, Y., Fujimoto, T., Sekiguchi, R., Uenaka, K., Callies, S., et al. (2011). Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 68, 505–511.CrossrefGoogle Scholar

  • Tavassoli, M., Guelen, L., Luxon, B.A, and Gäken, J. (2005). Apoptin: specific killer of tumor cells? Apoptosis 10, 717–724.CrossrefPubMedGoogle Scholar

  • Taylor, S.M. and Jones, P.A. (1982). Changes in phenotypic expression in embryonic and adult cells treated with 5-azacytidine. J. Cell Physiol. 111, 187–194.CrossrefGoogle Scholar

  • Teitz, T., Wei, T., Valentine, M.B., Vanin, E.F., Grenet, J., Valentine, V.A., Behm, F.G., Look, A.T., Lahti, J.M., et al. (2000). Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat. Med. 6, 529–535.Google Scholar

  • Tekautz, T.M., Zhu, K., Grenet, J., Kaushal, D., Kidd, V.J., and Lahti, J.M. (2006). Evaluation of IFN-gamma effects on apoptosis and gene expression in neuroblastoma – preclinical studies. Biochim. Biophys. Acta 1763, 1000–1010.Google Scholar

  • Thiele, C.J., Reynolds, C.P., and Israel, M.A. (1985). Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. Nature 313, 404–406.Google Scholar

  • Teodoro, J.G., Heilman, D.W., Parker, A.E., and Green, M.R. (2004). The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53. Genes Dev. 18, 1952–1957.Google Scholar

  • Tolcher, A.W., Mita, A., Lewis, L.D., Garrett, C.R., Till, E., Daud, A.I., Patnaik, A., Papadopoulos, K., Takimoto, C., Bartels, P., et al. (2008). Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivin. J. Clin. Oncol. 26, 5198–5203.Google Scholar

  • Tsuruma, T., Hata, F., Torigoe, T., Furuhata, T., Idenoue, S., Kurotaki, T., Yamamoto, M., Yagihashi, A., Ohmura, T., Yamaguchi, K., et al. (2004). Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. J. Transl. Med. 2, 19.PubMedCrossrefGoogle Scholar

  • Velculescu, V.E., Madden, S.L., Zhang, L., Lash, A.E., Yu, J., Rago, C., Lal, A., Wang, C.J., Beaudry, G.A., Ciriello, K.M., et al. (1999). Analysis of human transcriptomes. Nat. Genet. 23, 387–388.CrossrefPubMedGoogle Scholar

  • Wang, R.H., Zheng, Y., Kim, H.S., Xu, X., Cao, L., Luhasen, T., Lee, M.H., Xiao, C., Vassilopoulos, A., Chen, W., et al. (2008). Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol. Cell 32, 11–20.CrossrefGoogle Scholar

  • Wang, L., Chen, S., Xue, M., Zhong, J., Wang, X., Gan, L., Lam, E.K., Liu, X., Zhang, J., Zhou, T., et al. (2012). Homeobox D10 gene, a candidate tumor suppressor, is downregulated through promoter hypermethylation and associated with gastric carcinogenesis. Mol. Med. 18, 389–400.Google Scholar

  • Wiley, S.R., Schooley, K., Smolak, P.J., Din, W.S., Huang, C.P., Nicholl, J.K., Sutherland, G.R., Smith, T.D., Rauch, C., and Smith, C.A. (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.PubMedCrossrefGoogle Scholar

  • Wu, Y., Alvarez, M., Slamon, D.J., Koeffler, P., and Vadgama, J.V. (2010). Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation. BMC Cancer. 10, 32.CrossrefGoogle Scholar

  • Xiaojiang, T., Jinsong, Z., Jiansheng, W., Chengen, P., Guangxiao, Y., and Quanying, W. (2010). Adeno-associated virus harboring fusion gene NT4-ant-shepherdin induce cell death in human lung cancer cells. Cancer Invest. 28, 465–471.CrossrefGoogle Scholar

  • Xie, X., Zhao, X., Liu, Y., Zhang, J., Matusik, R.J., Slawin, K.M., and Spencer, D.M. (2001). Adenovirus-mediated tissue-targeted expression of a caspase-9-based artificial death switch for the treatment of prostate cancer. Cancer Res. 61, 6795–6804.Google Scholar

  • Yamanaka, K., Nakahara, T., Yamauchi, T., Kita, A., Takeuchi, M., Kiyonaga, F., Kaneko, N., and Sasamata, M. (2011). Antitumor activity of YM155, a selective small-molecule survivin suppressant, alone and in combination with docetaxel in human malignant melanoma models. Clin. Cancer Res. 17, 5423–5431.CrossrefGoogle Scholar

  • Yang, X., Merchant, M.S., Romero, M.E., Tsokos, M., Wexler, L.H., Kontny, U., Mackall, C.L., and Thiele, C.J. (2003). Induction of caspase 8 by interferon gamma renders some neuroblastoma (NB) cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membrane TR1/TR2 also contributes to TRAIL resistance in NB. Cancer Res. 63, 1122–1129.Google Scholar

  • Ye, J., Ortaldo, J.R., Conlon, K., Winkler-Pickett, R., and Young, H.A. (1995). Cellular and molecular mechanisms of IFN-γ production induced by IL-2 and IL-12 in a human NK cell line. J. Leukoc Biol. 58, 225–233.Google Scholar

  • Yoon, D.H., Shin, J.S., Jin, D.H., Hong, S.W., Jung, K.A., Kim, S.M., Hong, Y.S., Kim, K.P., Lee, J.L., Suh, C., et al. (2012). The survivin suppressant YM155 potentiates chemosensitivity to gemcitabine in the human pancreatic cancer cell line MiaPaCa-2. Anticancer Res. 32, 1681–1688.PubMedGoogle Scholar

  • Zaidi, M.R. and Merlino, G. (2011). The two faces of interferon-γ in cancer. Clin. Cancer Res. 17, 6118–6124.PubMedCrossrefGoogle Scholar

  • Zhang, X.D., Franco, A., Myers, K., Gray, C., Nguyen, T., and Hersey, P. (1999a). Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma. Cancer Res. 59, 2747–2753.PubMedGoogle Scholar

  • Zhang, Y.H., Abrahams, P.J., van der, Eb A.J., and Noteborn, M.H. (1999b). The viral protein Apoptin induces apoptosis in UV-C-irradiated cells from individuals with various hereditary cancer-prone syndromes. Cancer Res. 59, 3010–3015.Google Scholar

  • Zhang, Y.H., Leliveld, S.R., Kooistra, K., Molenaar, C., Rohn, J.L., Tanke, H.J., Abrahams, J.P., and Noteborn, M.H. (2003). Recombinant Apoptin multimers kill tumor cells but are nontoxic and epitope-shielded in a normal-cell-specific fashion. Exp. Cell Res. 289, 36–46.Google Scholar

About the article

Patrick Hensley

Patrick Hensley is a medical student at the University of Kentucky College of Medicine. He earned a Bachelor of Science degree from Miami University, Oxford, Ohio in 2010. Patrick is currently completing a one year fellowship in the Department of Pathology where he is refining his interests in surgical and molecular oncology. Patrick has spent three years studying novel therapeutics for the treatment of advanced-stage prostate cancer and will pursue residency training in urologic oncology and pathology.

Murli Mishra

Murli Mishra is a 2nd year graduate student at Graduate Center for Toxicology, College of Medicine, University of Kentucky. He completed his MS (Pharm) with major Regulatory Toxicology from National Institute of Pharmaceutical Education & Research (NIPER), Mohali, India. He completed his bachelor degree in Pharmacy from Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, India. His long term goal is to become a researcher and explore molecular toxicology and cancer biology.

Natasha Kyprianou

Dr. Natasha Kyprianou is a Professor of Urology, Molecular Biochemistry, Pathology and Toxicology and holds the James F. Hardymon Chair in Urology Research at the University of Kentucky College of Medicine, Lexington, Kentucky. She received her undergraduate and medical school education at the University of London and the University of Leeds, and completed her doctoral studies at the University of Wales College of Medicine in the United Kingdom. Dr. Kyprianou completed fellowships in Molecular Oncology at Johns Hopkins University School of Medicine and in Molecular Biology at the Imperial Cancer Research Fund in London, England. Her research interests focus on the deregulation of apoptosis and growth factor signaling pathways in urologic malignancies and development of molecular therapeutics (via tumor selective apoptosis-targeting) for castration-resistant prostate tumors and novel biomarkers of prostate and bladder cancer metastasis.


Corresponding author: Natasha Kyprianou, Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA; Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA; and Graduate Center for Toxicology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA


Received: 2013-01-28

Accepted: 2013-03-15

Published Online: 2013-03-18

Published in Print: 2013-07-01


Citation Information: Biological Chemistry, Volume 394, Issue 7, Pages 831–843, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0128.

Export Citation

©2013 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Marina Teras, Edda Viisileht, Merlis Pahtma-Hall, Airi Rump, Viiu Paalme, Pille Pata, Illar Pata, Christelle Langevin, and Sirje Rüütel Boudinot
BMC Cancer, 2018, Volume 18, Number 1
[2]
Yang Wang, Xu Deng, Chang Yu, Guosheng Zhao, Jing Zhou, Ge Zhang, Ming Li, Dianming Jiang, Zhengxue Quan, and Yuan Zhang
Journal of Experimental & Clinical Cancer Research, 2018, Volume 37, Number 1
[3]
Shilpa Kuttikrishnan, Kodappully S. Siveen, Kirti S. Prabhu, Abdul Quaiyoom Khan, Sabah Akhtar, Jericha M. Mateo, Maysaloun Merhi, Ruba Taha, Halima El Omri, Fatima Mraiche, Said Dermime, and Shahab Uddin
Leukemia & Lymphoma, 2018, Page 1
[4]
Kirti S. Prabhu, Kodappully Sivaraman Siveen, Shilpa Kuttikrishnan, Ahmad N. Iskandarani, Abdul Q. Khan, Maysaloun Merhi, Halima E. Omri, Said Dermime, Tamam El-Elimat, Nicholas H. Oberlies, Feras Q. Alali, and Shahab Uddin
Frontiers in Pharmacology, 2018, Volume 9
[5]
Juyoung Kim, Kyung Hee Jung, Hong Hua Yan, Min Ji Cheon, Sunmi Kang, Xing Jin, Sunghyouk Park, Myung Sook Oh, and Soon-Sun Hong
BMC Complementary and Alternative Medicine, 2018, Volume 18, Number 1
[6]
Derek Cui Xu, Lewis Arthurton, and Luis Alberto Baena-Lopez
BioMed Research International, 2018, Volume 2018, Page 1
[7]
Jing Zhang, Likun Liu, Jing Wang, Baoyin Ren, Lin Zhang, and Weiling Li
Journal of Ethnopharmacology, 2018
[8]
Liying Shi, Haihong Qin, Xudong Jin, Xiuxiu Yang, Xuan Lu, Huiguo Wang, Ruoyu Wang, Dayong Yu, and Baomin Feng
Biomedicine & Pharmacotherapy, 2018, Volume 102, Page 772
[9]
Takuhiro Uto, Nguyen Huu Tung, Tomoe Ohta, Wipawee Juengsanguanpornsuk, Le Quoc Hung, Nguyen Thanh Hai, Dinh Doan Long, Phuong Thien Thuong, Shinya Okubo, Sakiko Hirata, and Yukihiro Shoyama
Phytotherapy Research, 2018
[10]
Xumin Zhou, Jumei Liu, Jinming Zhang, Yong Wei, and Hua Li
Cell Death Discovery, 2018, Volume 4, Number 1
[11]
Andra Banete, Kyle Seaver, Devyani Bakshi, Katrina Gee, and Sameh Basta
Journal of Leukocyte Biology, 2018
[12]
Fangfei Niu, Yonghua Liu, Zongpan Jing, Gaijing Han, Lianqi Sun, Lu Yan, Lanping Zhou, Yanbin Wu, Yang Xu, Laixing Hu, and Xiaohang Zhao
Cancer Letters, 2018
[13]
KENZO SONODA
Oncology Letters, 2016, Volume 11, Number 1, Page 16
[14]
Shuhua Jiao, Nuo Li, Shuang Cai, Haimei Guo, and Yanhui Wen
Oncology Letters, 2017, Volume 13, Number 4, Page 2133
[15]
Yuan Zhang, Xu Deng, Tao Lei, Chang Yu, Yang Wang, Guosheng Zhao, Xiaoji Luo, Ke Tang, Zhengxue Quan, and Dianming Jiang
Oncology Reports, 2017, Volume 38, Number 5, Page 2685
[16]
CHEOL PARK, JI-SUK JEONG, JIN-WOO JEONG, YONG-JOO KIM, YEON-KWON JUNG, GEUN-BAE GO, SUNG OK KIM, GI-YOUNG KIM, SU-HYUN HONG, YOUNG HYUN YOO, and YUNG HYUN CHOI
International Journal of Oncology, 2016, Volume 48, Number 1, Page 261
[17]
Luis Alberto Baena-Lopez, Lewis Arthurton, Derek Cui Xu, and Alessia Galasso
Seminars in Cell & Developmental Biology, 2017
[18]
MOON HEE LEE, SU-HYUN HONG, CHEOL PARK, GI-YOUNG KIM, SUN-HEE LEEM, SUNG HYUN CHOI, YOUNG-SAM KEUM, JIN WON HYUN, TAEG KYU KWON, SANG HOON HONG, and YUNG HYUN CHOI
Oncology Reports, 2016, Volume 36, Number 1, Page 205
[19]
Eun-Ok Choi, Cheol Park, Hye-Jin Hwang, Su Hyun Hong, Gi-Young Kim, Eun-Ju Cho, Wun-Jae Kim, and Yung Hyun Choi
International Journal of Oncology, 2016, Volume 49, Number 3, Page 1009
[20]
JIAO NIE, CHANGLIN ZHAO, LI DENG, JIA CHEN, BIN YU, XIANLIN WU, PENG PANG, and XIAOYIN CHEN
Biomedical Reports, 2016, Volume 4, Number 1, Page 3
[21]
Moon Hee Lee, Hee-Jae Cha, Eun Ok Choi, Min Ho Han, Sung Ok Kim, Gi-Young Kim, Su Hyun Hong, Cheol Park, Sung-Kwon Moon, Soon-Jeong Jeong, Moon-Jin Jeong, Wun-Jae Kim, and Yung Hyun Choi
International Journal of Molecular Medicine, 2017, Volume 39, Number 3, Page 672
[22]
Fatemeh Hajiaghaalipour, Elham Bagheri, Fadhil Lafta Faraj, Mahmood Ameen Abdulla, and Nazia Abdul Majid
RSC Adv., 2017, Volume 7, Number 61, Page 38257
[23]
Zhihong Yuan, Mansoor Ali Syed, Dipti Panchal, Myungsoo Joo, Marco Colonna, Mark Brantly, and Ruxana T. Sadikot
Journal of Biological Chemistry, 2014, Volume 289, Number 21, Page 15118
[25]
Xiaoxv Dong, Jing Fu, Xingbin Yin, Chunjing Yang, and Jian Ni
Phytotherapy Research, 2017, Volume 31, Number 6, Page 927
[26]
Mashitoh Abd Rahman, Faiqah Ramli, Hamed Karimian, Firouzeh Dehghan, Noraziah Nordin, Hapipah Mohd Ali, Syam Mohan, Najihah Mohd Hashim, and Irina V Lebedeva
PLOS ONE, 2016, Volume 11, Number 3, Page e0151466
[27]
Patrick J. Hensley, Andreas Desiniotis, Chi Wang, Arnold Stromberg, Ching-Shih Chen, Natasha Kyprianou, and Lucia R. Languino
PLoS ONE, 2014, Volume 9, Number 1, Page e86238
[28]
You-Guang Zheng, Jun Su, Cai-Yun Gao, Ping Jiang, Lin An, Yun-Sheng Xue, Jian Gao, and Yi Liu
European Journal of Medicinal Chemistry, 2017, Volume 130, Page 393
[29]
Alethéia L. Silveira, Glaúcia V. Faheina-Martins, Raquel C. Maia, Demetrius A. M. Araújo, and Arun Rishi
PLoS ONE, 2014, Volume 9, Number 9, Page e107404
[30]
Cheol Park, Min-Ho Han, Shin-Hyung Park, Su-Hyun Hong, Gi-Young Kim, Sung-Kwon Moon, Wun-Jae Kim, and Yung Hyun Choi
Revista Brasileira de Farmacognosia, 2017, Volume 27, Number 3, Page 315
[31]
Seon Young Park, Cheol Park, Shin-Hyung Park, Su-Hyun Hong, Gi-Young Kim, Sang Hoon Hong, and Yung-Hyun Choi
BioScience Trends, 2016, Volume 10, Number 6, Page 467
[32]
Dayong Yu, Xiuxiu Yang, Xuan Lu, Liying Shi, and Baomin Feng
Biomedicine & Pharmacotherapy, 2016, Volume 84, Page 1802
[33]
Jen-Jie Lin, Robert Wang, Jiing-Chuan Chen, Chien-Chih Chiu, Ming-Hui Liao, and Yu-Jen Wu
International Journal of Molecular Sciences, 2016, Volume 17, Number 12, Page 1787
[34]
Tae Kyung Lee, Cheol Park, Soon-Jeong Jeong, Moon-Jin Jeong, Gi-Young Kim, Wun-Jae Kim, and Yung Hyun Choi
Drug Development Research, 2016, Volume 77, Number 5, Page 227
[35]
Hye Park, Gi-Young Kim, Sung-Kwon Moon, Wun Kim, Young Yoo, and Yung Choi
Molecules, 2014, Volume 19, Number 5, Page 5981
[36]
Yaqiong Zu, Zhiyong Yang, Songshan Tang, Ying Han, and Jun Ma
Molecules, 2014, Volume 19, Number 9, Page 13061
[37]
[38]
ZHENNI WANG, YAPING LV, JUN XIA, HAO SHI, WEIZHONG WANG, and YONGLIE ZHOU
Molecular Medicine Reports, 2015, Volume 12, Number 3, Page 3537
[39]
YO-SEOB SEO, MIN-JI YIM, BOK-HEE KIM, KYUNG-ROK KANG, SOOK-YOUNG LEE, JI-SU OH, JAE-SEEK YOU, SU-GWAN KIM, SANG-JOUN YU, GYEONG-JE LEE, DO KYUNG KIM, CHUN SUNG KIM, JIN-SOO KIM, and JAE-SUNG KIM
Oncology Reports, 2015, Volume 34, Number 6, Page 3025
[40]
Juanjuan Yi, Zhenyu Wang, Haina Bai, Lu Li, Haitian Zhao, Cuilin Cheng, Hua Zhang, and Jingtong Li
RSC Adv., 2016, Volume 6, Number 7, Page 5278
[41]
Min Guo, Guo-Bin Ding, Songjia Guo, Zhuoyu Li, Liangqi Zhao, Ke Li, and Xiangrong Guo
Food Funct., 2015, Volume 6, Number 9, Page 3035
[42]
Takuhiro Uto, Nguyen Huu Tung, Regina Appiah-Opong, Abigail Aning, Osamu Morinaga, Dominic Edoh, Alexander K. Nyarko, and Yukihiro Shoyama
The American Journal of Chinese Medicine, 2015, Volume 43, Number 04, Page 757
[43]
Chuan Cai, Rui Zhang, Qiao-ying Huang, Xu Cao, Liang-yu Zou, and Xiao-fan Chu
Journal of Huazhong University of Science and Technology [Medical Sciences], 2015, Volume 35, Number 3, Page 397
[44]
Igor A. Sobenin, Yuri V. Bobryshev, Gleb A. Korobov, Evgeny N. Borodachev, Anton Y. Postnov, and Alexander N. Orekhov
Experimental and Molecular Pathology, 2015, Volume 99, Number 1, Page 1
[45]
Veronica G. Anania and Jennie R. Lill
PROTEOMICS - Clinical Applications, 2015, Volume 9, Number 7-8, Page 671
[46]
XIAOLI MA, HUA DUAN, JIA LIU, QINGQING MO, CHENGJUAN SUN, DING MA, and JIANDONG WANG
Oncology Reports, 2015, Volume 33, Number 2, Page 893
[48]
Henrique J. Cardoso, Cátia V. Vaz, Sara Correia, Marília I. Figueira, Ricardo Marques, Cláudio J. Maia, and Sílvia Socorro
The Prostate, 2015, Volume 75, Number 9, Page 923
[49]
Gledy Negrín, Sara Rubio, María Teresa Marrero, José Quintana, José Luis Eiroa, Jorge Triana, and Francisco Estévez
Phytomedicine, 2015, Volume 22, Number 3, Page 385
[50]
Mi-Ra Park, Su-Gwan Kim, In-A. Cho, Dahye Oh, Kyeong-Rok Kang, Sook-Young Lee, Sung-Min Moon, Seung Sik Cho, Goo Yoon, Chun Sung Kim, Ji-Su Oh, Jae-Seek You, Do Kyung Kim, Yo-Seob Seo, Hee-Jeong Im, and Jae-Sung Kim
Food and Chemical Toxicology, 2015, Volume 77, Page 34
[51]
Ran Yao, Zhaoli Chen, Chengcheng Zhou, Mei Luo, Xuejiao Shi, Jiagen Li, Yibo Gao, Fang Zhou, Jianxin Pu, Handong Sun, and Jie He
Journal of Natural Products, 2015, Volume 78, Number 1, Page 10
[52]
Stian Sjøli, Ann Iren Solli, Øyvind Akselsen, Yang Jiang, Eli Berg, Trond Vidar Hansen, Ingebrigt Sylte, and Jan-Olof Winberg
Biochimica et Biophysica Acta (BBA) - General Subjects, 2014, Volume 1840, Number 10, Page 3162
[54]
Ronald-Allan Panganiban, Andrew Snow, and Regina Day
International Journal of Molecular Sciences, 2013, Volume 14, Number 8, Page 15931
[56]
Shalise M. Couvertier and Eranthie Weerapana
Med. Chem. Commun., 2014, Volume 5, Number 3, Page 358
[57]
Onat Kadioglu, Navid Salehi Kermani, Gerhard Kelter, Udo Schumacher, Heinz-Herbert Fiebig, Henry Johannes Greten, and Thomas Efferth
Biochemical Pharmacology, 2014, Volume 87, Number 3, Page 399

Comments (0)

Please log in or register to comment.
Log in