title: Resveratrol suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway.
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.
authors.affiliation: College of Applied Medical Sciences, Qassim University, Buraidah, Al-Qassim, Saudi Arabia. Electronic address: arifbiotech@gmail.com.
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
authors.affiliation: College of Applied Medical Sciences, Qassim University, Buraidah, Al-Qassim, Saudi Arabia.
authors.forename: Ahmad N
authors.initials: AN
authors.lastname: Aljarbou
authors.affiliation: College of Applied Medical Sciences, Qassim University, Buraidah, Al-Qassim, Saudi Arabia.
authors.forename: Yousef H
authors.initials: YH
authors.lastname: Aldebasi
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Faisal
authors.affiliation: College of Applied Medical Sciences, Qassim University, Buraidah, Al-Qassim, Saudi Arabia.
authors.forename: Masood A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077185:Resveratrol; D013267:Stilbenes; C508053:ERBB2 protein, human
keywords: Akt; FASN; Her2; PI3K; Resveratrol; SKBR-3