Benzoquinone from Fusarium pigment inhibits the proliferation of estrogen receptor-positive MCF-7 cells through the NF-κB pathway via estrogen receptor signaling

摘要

Natural pigments are known for possessing a wide range of pharmacological and health-promoting properties. The pigments, produced by a new strain Fusarium (Fusarium sp. JN158) previously identified in our laboratory, were found to have 6 peaks (representing 6 compounds) by high-performance liquid chromatography with a diode-array detector (HPLC-DAD) separation. The 6th peak compound (compound VI) is a benzoquinone compound. In this study, we examined the effects of compound VI on the proliferation of breast cancer cells and aimed to elucidate the underlying mechamisms. Compound VI exerted anti-proliferative effects on MCF-7 estrogen receptor (ER)⁺ cells in a dose-dependent manner (IC25, 7 µM; IC50, 11 µM), whereas it had no effect on MDA-MB-231 ER⁻ cells and normal cells. The cell index (CI) began to decrease at 24 h following treatment with benzoquinone. Mechanistically, the results from molecular analysis revealed that compound VI inhibited the expression of ERα, progesterone receptor (PR), vascular endothelial growth factor (VEGF), Bcl-2, cyclin D1 and nuclear factor-κB (NF-κB) p65, while it increased the expression of cleaved caspase-3 and Bax in the MCF-7 cells. Taken together, our findings indicate that compound VI exerts anti-proliferative effects on MCF-7 cells through the NF-κB pathway via the regulation of ER signaling. Our data may indicate that benzoquinone from Fusarium pigment may have potential for use as an anti-proliferative agent in the treatment of breast cancer.