Growth-inhibiting and apoptosis-inducing effects of Tanshinone II A on human gastric carcinoma cells

Abstract

To explore the effects of Tanshinone II A on the proliferation, apoptosis and gene expression of p53 and bcl-2 in human gastric carcinoma MKN-45 cells. Cell count and MTT assay were used to study the proliferation-inhibiting effect of Tanshinone II A on MKN-45 cells. The effect of Tanshinone II A on the cell cycle and apoptosis of MKN-45 cells were examined by propidium iodide (PI) staining and flow cytometry. Semi-quantitative RT-PCR was used to further verify the expression of p53 and bcl-2 gene after exposure to Tanshinone A in MKN-45 cells. The results showed that Tanshinone A significantly inhibited the growth and proliferation of MKN-45 cells in a dose-and time-dependent manner (P<0.05). Tanshinone A arrested MKN-45 cells in G₂/M phase which led to an obvious accumulation of G₂/M phase cells while decreased number of G₀/G₁ phase cells. This resulted in apoptosis of MKN-45 cells and the apoptosis rate was as high as 43.91% after treatment with 2.0 μg/mL Tanshinone II A for 96 h. It was also found that Tanshinone II A up-regulated expression of p53 gene and down-regulated expression of bcl-2 gene. The cytostatic and antiproliferative effect of Tanshinone II A makes it a promising anticancer agent for the treatment of gastric carcinoma.

Keywords

tanshinone II A / human gastric carcinoma / apoptosis / cell cycle

References

[1] ParkinD. M., BrayF. I., DevesaS. S.. Cancer burden in the year 2000. The global picture. Eur J Cancer, 2001, 37(Suppl8): S4-S66

[2] YuanS. L., WeiY. Q., WangX. J., et al.. Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. World J Gastroenterol, 2004, 10(14): 2024-2028

[3] WangH., GaoX., ZhangB.. Tanshinone: an inhibitor of proliferation of vascular smooth muscle cells. J Ethnopharmacol, 2005, 99(1): 93-98

[4] HuH., ZhangY., HuangF., et al.. Inhibition of proliferation and induction of apoptosis by tanshinone II A in NCI-H460 cell. Zhong Yao Cai (Chinese), 2005, 28(4): 301-304

[5] WangX., WeiY., YuanS., et al.. Potential anticancer activity of tanshinone II A against human breast cancer. Int J Cancer, 2005, 116(5): 799-807

[6] YoonY., KimY. O., JeonW. K., et al.. Tanshinone IIA isolated from Salvia miltiorrhiza Bunge induced apoptosis in HL60 human premyelocytic leukemia cell line. J Ethnopharmacol, 1999, 68(1–3): 121-127

[7] LiangY., SongW. X., WangJ., et al.. A study on the cell differentiation induced by tanshinone IIA and its molecular mechanism in retinoic acid: resistant acute promyelocytic leukemia. Zhonghua Nei Ke Za Zhi (Chinese), 2005, 44(5): 366-369

[8] SelvakumaranM., PisarcikD. A., BaoR., et al.. Enhanced cisplatin cytotoxicity by disturbing the nucleotide excision repair pathway in ovarian cancer cell lines. Cancer Res, 2003, 63(6): 1311-1316

[9] HyunJ. S., SunM. C., YoosikY., et al.. Tanshinone II A, an ingredient of Salvia miltiorrhiza Bunge, induces apoptosis in human leukemia cell lines through the activation of caspase-3. Exp Mol Med, 1999, 31(4): 174-178

[10] IkeguchiM., TatebeS., KaibaraN., et al.. Changes in levels of expression of p53 and the product of the bcl-2 in lines of gastric cancer cells during cisplatin-induced apoptosis. Eur Surg Res, 1997, 29(5): 396-402