title: FoxO3a is Essential for the Antiproliferative and Apoptogenic Effects of Sunitinib in MDA-MB231 Cell Line.
abstract: Sunitinib (SUN), a tyrosine kinase inhibitor, is a promising treatment for triple-negative breast cancer (TNBC), the most aggressive and fast-growing type of breast cancer. Yet, the protective effect of SUN against TNBC is poorly investigated and the role of Forkhead box type O (FOXO3a) transcription factor is still unknown.
  
  
  
  Cell proliferation was evaluated using the MTT assay. The mRNA and protein expression of apoptotic, oxidative stress and cell cycle genes were determined by real-time polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Percentage of the apoptotic cells were determined by flow cytometry. The role of FOXO3a was knock-downed using siRNA.
  
  
  
  SUN caused suppression of MDA-MB231 cell growth associated with induction of apoptosis, cell cycle arrest, oxidative stress markers and FOXO3a gene. Importantly, silencing of FOXO3a mRNA using siRNA significantly rescued MDA-MB231 cells from SUN-induced cell-proliferative arrest.
  
  
  
  SUN inhibits TNBC MDA-MB231 cell proliferation through activation of FOXO3a expression.
authors: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia hkorashy@ksu.edu.sa.
authors: Hesham M
authors: HM
authors: Korashy
authors: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors: Osamah M
authors: OM
authors: Belali
authors: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors: Mushtaq A
authors: MA
authors: Ansar
authors: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors: Naif O
authors: NO
authors: Alharbi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: FOXO3a; MDA-MB231 cells; Sunitinib; apoptosis; cyclin D; oxidative stress