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.
BackgroundTumor metastasis with poor prognosis is still the leading cause of deaths among triple-negative breast caner (TNBC) patients. Therefore, understanding the underlying molecular mechanisms of TNBC metastasis and identifying the molecules contributing to the process are of great importance.It would be provided targets for the prevention and treatment of recurrence and metastasis of TNBC. MethodsThe expression level of MAP3K1 and its up-or downstream genes,SOX2 and KLF4 were detected using Western blotting assay. Cell migration and proliferation were measure by xCELLigence Real-Time Cell Analyzer (RTCA). Protein interaction was used for co-immunorecipitation. ResultCompared with metastasis (Met) in TBNC model, the expression of MAP3K1,KLF4,ERK1/2, C-jun and werelower, while SOX2, Ras,Rafand c-Fos were higher in non-metastasis (non-Met) samples. In MAP3K1 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were increased. The expression level of KLF4 was lower than SOX2 reduced or minimal interaction of both. In SOX2 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were decreased, while the expression of KLF4 and MAP3K1 were higher, the interaction of MAP3K1 and KLF4 was inhibited. ConclusionsIt is demonstrated for the very first time that SOX2 and MAP3K1 are playing an important rolesin TNBC cell metastasis by regulating MAPK signaling pathway by interacting with KLF4 .
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