Abstract
Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC50 values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans.
Highlights
Ovarian cancer is one of the most lethal gynecological cancers in the reproductive system of females, afflicting nearly 204,000 women per year and causing approximately 125,000 deaths [1].Due to a lack of effective biomarkers for screening, most patients with ovarian cancer are diagnosed at late stages
After treatment of ovarianbromide cells with galangin, effects of galangin theA2780/CP70 platinumand OVCAR-3 with galangin resulted in a concentration-dependent decrease in the cell viability over resistant ovarian cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe24 h
Using p53 Small Interfering RNA (siRNA) and PFT-α, we investigated the role of p53 on apoptosis induction in OVCAR-3 cells and found that the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% ± 3.5% to 10.2% ± 2.5% when treated with 20 μM PFT-α (Figure 6B)
Summary
Due to a lack of effective biomarkers for screening, most patients with ovarian cancer are diagnosed at late stages. The first-line therapy might cure 80% of patients with ovarian cancer, but the cancer. The first-line therapy might cure 80% of patients with ovarian cancer, but the cancer will recur in 70%. Those patients with aggressive or advanced tumors,tumors, with a limited for hope survival will recur in of of those patients with aggressive or advanced with a hope limited for [2]. Though platinum drugs most commonly used forovarian treatingcancer, ovarianpatients cancer, often have adverse side effects platinum drug drug therapy. MoreMore selective drugs are patients often have adverse side when effects receiving when receiving platinum therapy
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