KG-135 sensitizes human cervix carcinoma, HeLa cells to anti-cancer drugs via increasing expression level of p53 and Bax
Ginseng (Panax ginseng, C.A. Meyer) is one of the most widely used herbal medicines in oriental countries. Previous reports showed that Ginseng has cytostatic or cytotoxic activities against tumor cell culture and chronic administration of ginseng lowers incidence rates of some cancers. Here, we show that KG-135, a mixture containing same amount of three major red ginseng-specific ginsenosides, Rk1, Rg3 and Rg5, sensitizes cancer cells to anti-cancer drugs.
HeLa cells that are co-treated with 75µg/ml of KG-135 and low dose of anti-cancer drugs, etoposide or cisplatin becomes greatly sensitive to apoptosis than cells that were treated with the same dose of anti-cancer drug alone. In FACS analysis for co-treated HeLa cells, sub G1 peak was increased by over 4 fold and caspase-3 activity was also increased by about 2 fold higher as compared with those values in the cells that were treated with anti-cancer drug alone. The results from immunoblot assays indicate that co-treatment of KG-135 increases intracellular levels of p53 and Bax in the HeLa cells treated with the low dose of etoposide. However, this increase in the intracellular level of p53 is due not to transcriptional activation of p53, but to the increased stability of p53 by treatment of the cells with KG-135. After co-treatment of KG-135 and etoposide, Mitochondrial translocation of Bax was increased in parallel with increases in Bax-induced lost of mitochondrial Λψm. These results suggest that KG-135 sensitizes cancer cells to anti-cancer drugs via increasing the intracellular levels of p53 and that results in increases in mitochondrial translocation of Bax.
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