Scutellarin synergistically enhances cisplatin effect against ovarian cancer cells through enhancing the ability of cisplatin binding to DNA

摘要

Platinum resistance is a major limitation in the treatment of ovarian cancer. Combination of natural compounds with platinum-based agents is a new strategy for cancer chemotherapy. Recently, we found that scutellarin sensitized the anticancer effect of cisplatin to ovarian cancer cells. How scutellarin interacts with cisplatin and sensitizes its effect is unclear. Here, we found that the combination treatment of scutellarin and cisplatin enhanced apoptosis in ovarian cancer cells via increasing the extent of platinum-DNA adducts and the ratio of Bax/Bcl-2. The changes in UV-visible spectra indicated that scutellarin could form complex with cisplatin. Moreover, combination treatment prevented BamH1 digestion on pBR322 plasmid DNA more effectively suggesting that their interaction might cause a greater conformational change in the DNA, which finally induced the DNA strand breaks and enhanced apoptotic signaling pathway response. Our study supports that scutellarin acts as a potential sensitizer to cisplatin treatment and the combination of scutellarin and cisplatin may be a novel therapeutic strategy to overcome platinum resistance of ovarian cancer.