Abstract
Triple-negative breast cancer (TNBC) is an aggressive malignant neoplasia. The increased research interests in TNBC nowadays are due to the lack of clinically validated and molecular-targeted therapy. Fatty Acid Synthase (FASN) is the major biosynthetic enzyme for the synthesis of fatty acids from small carbon substrates. Elevated expression of FASN is frequent phenotypic alterations in many human cancers. The flavonoid Quercetin is one of the most abundant bioflavonoids in the human diet and a known inducer of apoptosis in several cancer cell lines. We aimed to evaluate the effects of Quercetin on TNBC in vitro and in vivo. Quercetin induced a significant growth-inhibitory effect against TNBC cells and the IC50 were 230 +/- 3 and 415 +/- 4 mu M for the TNBC cells, MDA-MB-231 and MDA-MB-157 respectively. Quercetin treatment induced anticancer/apoptotic effects against TNBC cells as shown by morphological alterations, DNA fragmentation, and caspase-3 activation. When compared to controls, decreased protein expression of FASN, beta-catenin, Bcl-2, and reduced-nuclear accumulation of beta-catenin were detected after Quercetin treatment. Quercetin in vivo-treatment induced significant tumor growth inhibition by 41.7% after 25 days of treatment. Immunohistochemical data showed a clear inhibition of FASN expression in tumor xenografts after Quercetin treatment. Quercetin possibly targets the lipogenic enzyme FASN and beta-catenin in TNBCs. Quercetin-induced apoptosis via targeting the de novo fatty acid synthesis is likely through a caspase-3 dependent mechanism coupled with modulation of FASN and beta-catenin expressions.