Abstract
To investigate the mechanism in Scutellarein-induced apoptosis of SAS human tongue cancer cells, inhibitory effects of Scutellarein on SAS cells were detected by MTT assay. Cell apoptosis was analyzed by flow cytometry. Ultrastructural changes of SAS cells were observed by transmission electron microscopy (TEM). Mitochondrial transmembrane potential (ΔΨm) were analyzed by JC-1 [5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide]. Western blotting was used to examine the expression level of Bcl-2, Bax and caspase-3 in SAS cells treated with Scutellarein. Scutellarein inhibited the proliferation of SAS cells in a time and dose-dependent manner and increased the percent of apoptotic cells. The mitochondrial cristae were swollen and had vacuolar degeneration. ΔΨm decreased when the concentration of scutellarein increased. Scutellarein effectively up-regulated the expression of mitochondrial Bax and caspase-3 and down-regulated the expression of Bcl-2. Scutellarein induces apoptosis of SAS human tongue cancer cells via activating mitochondrial signaling pathway.
[1] Myoung H, Kim MJ, Hong SD et al. Expression of membrane type I-matrix metalloproteinase in oral squamous cell carcinoma. Cancer Lett 2002; 185: 201–209 http://dx.doi.org/10.1016/S0304-3835(02)00281-110.1016/S0304-3835(02)00281-1Search in Google Scholar
[2] Miyazaki Y, Hara A, Kato K et al. The effect of hypoxic microenvironment on matrix metalloproteinase expression in xenografts of human oral squamous cell carcinoma. Int J Oncol 2008; 32: 145–151 10.3892/ijo.32.1.145Search in Google Scholar
[3] Panchal RG. Novel therapeutic strategies to selectively kill cancer cells. Biochem Pharmacol 1998; 55: 247–252 http://dx.doi.org/10.1016/S0006-2952(97)00240-210.1016/S0006-2952(97)00240-2Search in Google Scholar
[4] Sun MY, Zuo J, Duan JF et al. [Antitumor activities of kushen flavonoids in vivo and in vitro]. Zhong Xi Yi Jie He Xue Bao 2008; 6: 51–59 http://dx.doi.org/10.3736/jcim2008011110.3736/jcim20080111Search in Google Scholar PubMed
[5] Wang T, Zhang JC, Chen Y et al. [Comparison of antioxidative and antitumor activities of six flavonoids from Epimedium koreanum]. Zhongguo Zhong Yao Za Zhi 2007; 32: 715–718 Search in Google Scholar
[6] Lahiri-Chatterjee M, Katiyar SK, Mohan RR et al. A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res 1999; 59: 622–632 Search in Google Scholar
[7] Choi SU, Ryu SY, Yoon SK et al. Effects of flavonoids on the growth and cell cycle of cancer cells. Anticancer Res 1999; 19: 5229–5233 Search in Google Scholar
[8] Liu JJ, Huang TS, Cheng WF et al. Baicalein and baicalin are potent inhibitors of angiogenesis: Inhibition of endothelial cell proliferation, migration and differentiation. Int J Cancer 2003; 106: 559–565 DOI: 10.1002/ijc.11267 http://dx.doi.org/10.1002/ijc.1126710.1002/ijc.11267Search in Google Scholar PubMed
[9] Huang WH, Lee AR, Yang CH. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Biosci Biotechnol Biochem 2006; 70: 2371–2380 http://dx.doi.org/10.1271/bbb.5069810.1271/bbb.50698Search in Google Scholar PubMed
[10] Yu J, Lei J, Yu H et al. Chemical composition and antimicrobial activity of the essential oil of Scutellaria barbata. Phytochemistry 2004; 65: 881–884 DOI: 10.1016/j.phytochem.2004.02.005 http://dx.doi.org/10.1016/j.phytochem.2004.02.00510.1016/j.phytochem.2004.02.005Search in Google Scholar PubMed
[11] Wang CZ, Li XL, Wang QF et al. Selective fraction of Scutellaria baicalensis and its chemopreventive effects on MCF-7 human breast cancer cells. Phytomedicine 2010; 17: 63–68 DOI: 10.1016/j. phymed.2009.07.003 http://dx.doi.org/10.1016/j.phymed.2009.07.00310.1016/j.phymed.2009.07.003Search in Google Scholar PubMed PubMed Central
[12] Ye F, Che Y, McMillen E et al. The effect of Scutellaria baicalensis on the signaling network in hepatocellular carcinoma cells. Nutr Cancer 2009; 61: 530–537 DOI: 10.1080/01635580902803719 http://dx.doi.org/10.1080/0163558090280371910.1080/01635580902803719Search in Google Scholar PubMed
[13] Chen LG, Hung LY, Tsai KW et al. Wogonin, a bioactive flavonoid in herbal tea, inhibits inflammatory cyclooxygenase-2 gene expression in human lung epithelial cancer cells. Mol Nutr Food Res 2008; 52: 1349–1357 DOI: 10.1002/mnfr.200700329 http://dx.doi.org/10.1002/mnfr.20070032910.1002/mnfr.200700329Search in Google Scholar PubMed
[14] Liu XH, Kirschenbaum A, Yao S et al. Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 2000; 164: 820–825 http://dx.doi.org/10.1016/S0022-5347(05)67321-110.1016/S0022-5347(05)67321-1Search in Google Scholar
[15] Goh D, Lee YH, Ong ES. Inhibitory effects of a chemically standardized extract from Scutellaria barbata in human colon cancer cell lines, LoVo. J Agric Food Chem 2005; 53: 8197–8204 DOI: 10.1021/jf051506+ http://dx.doi.org/10.1021/jf051506+10.1021/jf051506+Search in Google Scholar PubMed
[16] Lee TK, Kim DI, Song YL et al. Differential inhibition of Scutellaria barbata D. Don (Lamiaceae) on HCG-promoted proliferation of cultured uterine leiomyomal and myometrial smooth muscle cells. Immunopharmacol Immunotoxicol 2004; 26: 329–342 http://dx.doi.org/10.1081/IPH-20002684110.1081/IPH-200026841Search in Google Scholar
[17] Lee SW, Song GS, Kwon CH et al. Beneficial effect of flavonoid baicalein in cisplatin-induced cell death of human glioma cells. Neurosci Lett 2005; 382: 71–75 DOI: 10.1016/j.neulet.2005.03.005 http://dx.doi.org/10.1016/j.neulet.2005.03.00510.1016/j.neulet.2005.03.005Search in Google Scholar PubMed
[18] Ma Z, Otsuyama K, Liu S et al. Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 2005; 105: 3312–3318 DOI: 10.1182/blood-2004-10-3915 http://dx.doi.org/10.1182/blood-2004-10-391510.1182/blood-2004-10-3915Search in Google Scholar PubMed
[19] Ujiki MB, Ding XZ, Salabat MR et al. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol Cancer 2006; 5: 76 http://dx.doi.org/10.1186/1476-4598-5-7610.1186/1476-4598-5-76Search in Google Scholar PubMed PubMed Central
[20] Way TD, Kao MC, Lin JK. Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem 2004; 279: 4479–4489 http://dx.doi.org/10.1074/jbc.M30552920010.1074/jbc.M305529200Search in Google Scholar PubMed
[21] Kim DI, Lee TK, Lim IS et al. Regulation of IGF-I production and proliferation of human leiomyomal smooth muscle cells by Scutellaria barbata D. Don in vitro: isolation of flavonoids of apigenin and luteolin as acting compounds. Toxicol Appl Pharmacol 2005; 205: 213–224 DOI: 10.1016/j. taap.2004.10.007 Search in Google Scholar
[22] Kim Jinh, Lee Eunok, Lee Hyoj et al. Caspase Activation and Extracellular Signal — Regulated Kinase/Akt Inhibition Were Involved in Luteolin — Induced Apoptosis in Lewis Lung Carcinoma Cells. Ann N Y Acad Sci 2007; 1095: 598–611 http://dx.doi.org/10.1196/annals.1397.102_210.1196/annals.1397.102_2Search in Google Scholar PubMed
[23] Zhang K, Guo QL, You QD et al. Wogonin induces the granulocytic differentiation of human NB4 promyelocytic leukemia cells and up-regulates phospholipid scramblase 1 gene expression. Cancer Sci 2008; 99: 689–695 DOI: 10.1111/j.1349-7006.2008.00728.x http://dx.doi.org/10.1111/j.1349-7006.2008.00728.x10.1111/j.1349-7006.2008.00728.xSearch in Google Scholar PubMed
[24] Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001; 411: 342–348 DOI: 10.1038/35077213 http://dx.doi.org/10.1038/3507721310.1038/35077213Search in Google Scholar PubMed
[25] Dixon S, Soriano B, Lush R et al. Apoptosis: its role in the development of malignancies and its potential as a novel therapeutic target. The Annals of pharmacotherapy 1997; 31: 76–82 10.1177/106002809703100113Search in Google Scholar
[26] Parajuli P, Joshee N, Rimando AM et al. In vitro an -titumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Med 2009; 75: 41–48 http://dx.doi.org/10.1055/s-0028-108836410.1055/s-0028-1088364Search in Google Scholar
[27] Hockenbery D, Nuñez G, Milliman C et al. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990; 348: 334–336 http://dx.doi.org/10.1038/348334a010.1038/348334a0Search in Google Scholar
[28] Ricci JE, Waterhouse N, Green DR. Mitochondrial functions during cell death, a complex (I-V) dilemma. Cell Death Differ 2003; 10: 488–492 DOI: 10.1038/sj.cdd.4401225 http://dx.doi.org/10.1038/sj.cdd.440122510.1038/sj.cdd.4401225Search in Google Scholar
[29] Reed JC, Green DR. Remodeling for demolition: changes in mitochondrial ultrastructure during apoptosis. Mol Cell 2002; 9: 1–3 http://dx.doi.org/10.1016/S1097-2765(02)00437-910.1016/S1097-2765(02)00437-9Search in Google Scholar
[30] Wang F, Ma R, Yu L. Role of mitochondria and mitochondrial cytochrome c in tubeimoside I-mediated apoptosis of human cervical carcinoma HeLa cell line. Cancer Chemother Pharmacol 2006; 57: 389–399 DOI: 10.1007/s00280-005-0047-y http://dx.doi.org/10.1007/s00280-005-0047-y10.1007/s00280-005-0047-ySearch in Google Scholar PubMed
[31] Gardner CR. Anticancer drug development based on modulation of the Bcl-2 family core apoptosis mechanism. Expert Rev Anticancer Ther 2004; 4: 1157–1177 http://dx.doi.org/10.1586/14737140.4.6.115710.1586/14737140.4.6.1157Search in Google Scholar PubMed
[32] Kim KW, Jin UH, Kim DI et al. Antiproliferative effect of Scutellaria barbata D. Don. on cultured human uterine leiomyoma cells by down-regulation of the expression of Bcl-2 protein. Phytother Res 2008; 22: 583–590 DOI: 10.1002/ptr.1996 10.1002/ptr.1996Search in Google Scholar PubMed
[33] Chui CH, Lau FY, Tang JC et al. Activities of fresh juice of Scutellaria barbata and warmed water extract of Radix Sophorae Tonkinensis on anti-proliferation and apoptosis of human cancer cell lines. Int J Mol Med 2005; 16: 337–341 10.3892/ijmm.16.2.337Search in Google Scholar
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