Palmitate Enhances The Efficacy of Cisplatin And Doxorubicin Against Human Endometrial Carcinoma Cells

Abstract Background: Endometrial cancer is the most common gynecological cancer worldwide. 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. 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. Methods: Endometrial cancer cells were cultured with in vitro and treated with palmitate, doxorubicin, and cisplatin. Cell metabolic activity and combination index was measured using MTT assay. Protein expression was assessed with western blotting. Flow cytometry was used to examine the cell cycle profiles, cell proliferation, apoptosis, ROS, mitochondria membrane potential, and mitochondrial mass. Immunocytochemistry was used to investigate the mitochondrial morphology.Results: 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.Conclusion: This study provides a potential therapeutic strategy in which palmitate is used as an adjuvant in the treatment of endometrial cancer.