Flavonoids have been recently identified as a potential anticancer agent against various human epithelial cancers. In this study, the elucidation of mechanisms underlying the anticancer effects of the apigenin, luteolin and myricetin will be new knowledge about preventive strategies against epithelial ovarian cancer in which the effect of flavonoids is still unclear. The cytotoxic effect of flavonoids was assessed by MTT analysis of the ovarian cancer cells (A2780, OVCAR-3 and SKOV-3) in comparison to the ovarian epithelial cells (OSE). The intracellular reactive oxygen species (ROS) generation, malondialdehyde (MDA) and protein carbonyl levels, caspase-3 and -9 activities were evaluated using fluorescence spectrometry. Apoptosis and cell cycle arrest, and cell invasion were measured by flow cytometry and Boyden chamber assay, respectively. MTT analysis showed that flavonoids selectively decreased the cell viability of cancer cells. Furthermore, the intracellular ROS generation was induced or scavenged by flavonoids depending on the structural differences. The flavonoids increased MDA levels due to the disruption of the membrane. Caspase activities indicated that flavonoids activated the extrinsic apoptotic pathway when ROS was scavenged. In contrast, the induced intracellular ROS generation resulted in the activation of the intrinsic apoptotic pathway. In addition, the cell cycle was arrested in different cell cycle phases and cell invasion on the collagen was disrupted by flavonoids. The anticancer activities of apigenin, luteolin and myricetin were attributed to the alterations of ROS signaling, and as well as the induction of apoptosis, cell cycle arrest and abrogation of the invasion. The present study may uncover new strategies for ovarian cancer therapy.
Keywords: Cell cycle arrest; Cell death; Epithelial ovarian cancer; Flavonoids; Invasion; Reactive oxygen species.
Copyright © 2019. Published by Elsevier Masson SAS.