It has been documented that H2S, in some types of cancer, promotes tumor proliferation, whereas, in the other types, it inhibits the tumor cell growth. In the present study, we investigated the anti-cancer effects and relevant mechanisms of NaHS in C6 glioma cells. C6 cells were subjected to different concentrations of NaHS, then cell viability and morphological changes were examined by MTT assay and Hoechst staining. The protein expression of Caspase-3, Bcl-2, Bax, p38 MAPK (mitogen-activated protein kinase), and p53 was measured by Western blotting. This work demonstrated that NaHS could reduce cell number and induce apoptosis of C6 gliomas cells. The protein expression of Caspase-3 and Bax was up-regulated, while the protein expression of Bcl-2 was down-regulated. Additionally, p38 MAPK and p53 were activated in response to NaHS. Moreover, p38 MAPK inhibitor, SB203580, counteracted the inhibitory effect of NaHS on C6 glioma cells. These data suggest that NaHS can effectively reduce cell number of C6 cells by triggering the apoptosis via Caspase-dependent pathway. p38 MAPK and p53 play an important role in NaHS-induced apoptosis in C6 cells. These findings imply that administration of NaHS may represent a new strategy for the treatment of glioma.
The authors wish to thank Guodong GAO from Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, for the critical reading of the manuscript. Laboratory support from Jing Wang is also gratefully acknowledged. The authors would also like to thank Rong Kuang for her assistance with the molecular biology components of this work.
Conflicts of interest: None to declare.
Bansal, K., Liang, M.L., and Rutka, J.T. (2006). Molecular biology of human gliomas. Technol. Cancer Res. Treat. 5, 185–194. Search in Google Scholar
Derbal, Y. (2014). State machine modeling of MAPK signaling pathways. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2014, 5236–5239. Search in Google Scholar
Di Masi, A. and Ascenzi, P. (2013). H2S: a “double face” molecule in health and disease. Biofactors 39, 186–196. Search in Google Scholar
Goodenberger, M.L. and Jenkins, R.B. (2012). Genetics of adult glioma. Cancer Genet. 205, 613–621. Search in Google Scholar
Hao, Q. and Cho, W.C. (2014). Battle against cancer: an everlasting saga of p53. Int. J. Mol. Sci. 15, 22109–22127. Search in Google Scholar
Kashfi, K. (2014). Anti-cancer activity of new designer hydrogen sulfide-donating hybrids. Antioxid. Redox Signal. 20, 831–846. Search in Google Scholar
Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., and Kimura, H. (2013). Polysulfides are possible H2S-derived signaling molecules in rat brain. FASEB J. 27, 2451–2457. Search in Google Scholar
Lv, M., Li, Y., Ji, M.H., Zhuang, M., and Tang, J.H. (2014). Inhibition of invasion and epithelial-mesenchymal transition of human breast cancer cells by hydrogen sulfide through decreased phospho-p38 expression. Mol. Med. Rep. 10, 341–346. Search in Google Scholar
Ma, K., Liu, Y., Zhu, Q., Liu, C.H., Duan, J.L., Tan, B.K., and Zhu, Y.Z. (2011). H2S donor, S-propargyl-cysteine, increases CSE in SGC-7901 and cancer-induced mice: evidence for a novel anti-cancer effect of endogenous H2S? PLoS One 6, e20525. Search in Google Scholar
Perry, M.M., Hui, C.K., Whiteman, M., Wood, M.E., Adcock, I., Kirkham, P., Michaeloudes, C., and Chung, K.F. (2011). Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells. Am. J. Respir. Cell. Mol. Biol. 45, 746–752. Search in Google Scholar
Peti, W. and Page, R. (2013). Molecular basis of MAP kinase regulation. Protein Sci. 22, 1698–1710. Search in Google Scholar
Pflaum, J., Schlosser, S., and Muller, M. (2014). p53 Family and cellular stress responses in cancer. Front. Oncol. 4, 285. Search in Google Scholar
Shalini, S., Dorstyn, L., Dawar, S., and Kumar, S. (2015). Old, new and emerging functions of caspases. Cell Death Differ. 22, 526–539. Search in Google Scholar
Szabo, C. and Hellmich, M.R. (2013). Endogenously produced hydrogen sulfide supports tumor cell growth and proliferation. Cell Cycle 12, 2915–2916. Search in Google Scholar
Szabo, C. and Papapetropoulos, A. (2011). Hydrogen sulphide and angiogenesis: mechanisms and applications. Br. J. Pharmacol. 164, 853–865. Search in Google Scholar
Szabo, C., Coletta, C., Chao, C., Modis, K., Szczesny, B., Papapetropoulos, A., and Hellmich, M.R. (2013). Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. Proc. Natl. Acad. Sci. USA 110, 12474–12479. Search in Google Scholar
Szabo, C., Ransy, C., Modis, K., Andriamihaja, M., Murghes, B., Coletta, C., Olah, G., Yanagi, K., and Bouillaud, F. (2014). Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms. Br. J. Pharmacol. 171, 2099–2122. Search in Google Scholar
Vaux, D.L. and Korsmeyer, S.J. (1999). Cell death in development. Cell 96, 245–254. Search in Google Scholar
Young, P.R. (2013). Perspective on the discovery and scientific impact of p38 MAP kinase. J. Biomol. Screen 18, 1156–1163. Search in Google Scholar
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