Usnic acid-induced programmed cell death in ovarian cancer cells

Abstract

Usnic acid (UA) is a secondary metabolite obtained by lichen species and exerts a significant anti-proliferative effect on different cancer cells. The current study aimed to determine the efficiency of UA on ovarian cancer and reveal the underlying molecular mechanisms of UA mediated anti-cancer activity. In this study, the cytotoxic effect of UA was evaluated by xCELLigence real-time online cell analysis in OVCAR-3, A2780 ovarian cancer cells and L929 non-cancerous cell compared with Carboplatin. After treatment with IC50 concentration of UA, apoptosis, cell cycle analysis, mRNA expression levels, invasion, wound healing and metastasis assays were performed to evaluate of the molecular mechanism of the apoptosis pathway. UA showed more anti-proliferative effect than carboplatin on OVCAR-3 which is the most aggressive cell among ovarian cancer cells. UA significantly decreased the cell proliferation of OVCAR-3 cells through apoptosis and G0/G1 arrest. Additionally, UA inhibited the invasion and particularly the migration of OVCAR-3 cells compared with control. Moreover, the expression level of 63 target genes from 87 apoptosis associated genes in the primary panel was determined after IC50 concentration of UA in OVCAR-3 cells. UA caused apoptotic cell death through the extrinsic pathway and over-expression of p53. Our findings demonstrated that UA-induced early and late apoptosis through G0/G1 arrest and extrinsic apoptosis signaling pathways and inhibited the migration and invasion of OVCAR-3 cells. Therefore, UA as a novel candidate molecule may be used for the treatment of ovarian cancer.Graphical abstractUsnic acid (UA) exerts anti-cancer effects and induces apoptosis through the extrinsic pathway and over-expression of p53. Additionally, UA potentially inhibits the migration ability of OVCAR-3 ovarian cancer cells. (Created with BioRender.com)