Palmitate Enhances the Efficacy of Cisplatin and Doxorubicin against Human Endometrial Carcinoma Cells

Abstract

Endometrial cancer is the most common gynecological cancer worldwide. At present there is no effective screening test for its early detection and no curative treatment for women with advanced-stage or recurrent disease. Overexpression of fatty acid synthase is a common molecular feature of a subgroup of sex steroid-related cancers associated with poor prognoses, including endometrial cancers. Disruption of this fatty acid synthesis leads to cell apoptosis, making it a potential therapeutic target. The saturated fatty acid palmitate reportedly induces lipotoxicity and cell death by inducing oxidative stress in many cell types. Here, we explored the effects of palmitate combined with doxorubicin or cisplatin in the HEC-1-A and RL95-2 human endometrial cancer cell lines. The results showed that physiological concentrations of exogenous palmitate significantly increased cell cycle arrest, DNA damage, autophagy, and apoptosis in both RL95-2 and HEC-1-A cells. It also increased the chemosensitivity of both cell types. Notably, we did not observe that palmitate lipotoxicity reflected increased levels of reactive oxygen species, suggesting palmitate acts via a different mechanism in endometrial cancer. This study thus provides a potential therapeutic strategy in which palmitate is used as an adjuvant in the treatment of endometrial cancer.