hyperoside and Ovarian-Neoplasms

Cisplatin treatment some times leads to chemoresistance, which is now acknowledged partially due to the inductive expression of progesterone receptor membrane component (PGRMC)1 in ovarian cancer cells. PGRMC1 enhances autophagy, activates cytochrome p450, and inveigles signaling pathways to promote cell survival and reduce the effect of drug treatments. In this study, we give first line evidence that hyperoside inhibits cell viability, triggers autophagy and apoptosis in ovarian cancer cell lines. Mechanistically, PGRMC1-dependent autophagy was utilized by hyperoside to induce apoptotic cell death. Hyperoside induced the conversion of LC3B-I to LC3B-II and the formation of autophagosomes in ovarian cancer cells. Notably, PGRMC1 colocolized with LC3B‑II, and PGRMC1 overexpression enhanced hyperoside-induced autophagy and apoptosis, while PGRMC1 knockdown abrogated the action. Additionally, AKT signaling and Bcl-2 family were also involved in the hyperoside-induced autophagy and apoptosis. Importantly, in cisplatin-resistant ovarian cancer cells where PGRMC1 was overexpressed, hyperoside sensitized the cells to cisplatin treatment. Together these findings indicate hyperoside functions as a complementary therapy for ovarian cancer patients receiving platinum-based therapy.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Drug Resistance, Neoplasm; Female; Humans; Membrane Proteins; Ovarian Neoplasms; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Quercetin; Receptors, Progesterone; RNA Interference; RNA, Small Interfering; Signal Transduction