Oleanolic acid (OA), a pentacyclic triterpene acid widely distributed in food and traditional herbal remedies, exhibits diverse therapeutic effects. OA has been subjected to various chemical modifications to optimize its anticancer effect. Among other analogs, 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid (PFOA) was semisynthesized from OA. This study evaluates the cytotoxic effects of PFOA on MDA-MB-231, MCF-7, BT-474, and T-47D human breast cancer cells. Acute treatment of PFOA inhibited breast cancer cell viability in a dose-dependent manner. Treatment of PFOA at cytotoxic doses significantly induced apoptosis in cancer cells as shown by flow cytometry analysis. Activation of apoptosis in MCF-7 and BT-474 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8 and PARP-1, whereas apoptosis in MDA-MB-231 cells was initiated by the activation of caspase-9, caspase-3 and PARP-1. The mechanism of apoptosis induction in T-47D involves activation of PARP-1. PFOA decreased the expression of EGFR, HER-2, MET and ERα in human breast cancer cell lines. These findings suggest that PFOA inhibits cell growth, activates apoptosis, and decreases the expression of key proteins involved in progression of breast cancer.
Keywords: Apoptosis; Breast cancer; Caspase-8; Caspase-9; FAS ligand; Oleanolic acid.
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