Resveratrol suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway |
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Institution: | 1. Department of Medical Technology, Bethune Military Medical College, Shijiazhuang 050081, China;2. Department of Orthopedics, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China;3. Department of Pathobiology and Immunology, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050200, China;4. Tumor Research Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China;5. Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China;6. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;7. Clinical Trial Centre, Mater Medical Research Institute, Queensland 4101, Australia |
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Abstract: | In breast cancer cells, overexpression of human epidermal growth factor receptor 2 (HER2) increases the translation of fatty acid synthase (FASN) by altering the activity of PI3K/Akt signaling pathways. Cancer chemotherapy causes major side effects and is not effective enough in slowing down the progression of the disease. Earlier studies showed a role for resveratrol in the inhibition of FASN, but the molecular mechanisms of resveratrol-induced inhibition are not known. In the present study, we examined the novel mechanism of resveratrol on Her2-overexpressed breast cancer cells.The effect of resveratrol on the growth of breast cancer cells was assessed as percent cell viability by cytotoxicity-based MTT assay and the induction of apoptosis was determined by cell-death detection ELISA and flow cytometric analysis of Annexin-V–PI binding. Western immunobloting was used to detect signaling events in human breast cancer (SKBR-3) cells.Data showed that resveratrol-mediated down-regulation of FASN and HER2 genes synergistically induced apoptotic death in SKBR-3 cells. This concurrently caused a prominent up-regulation of PEA3, leads to down-regulation of HER2 genes. Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression.These findings suggest that resveratrol alters the cell cycle progression and induce cell death via FASN inhibition in HER2 positive breast cancer. |
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Keywords: | Akt FASN Her2 PI3K Resveratrol SKBR-3 |
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