Hesham M Korashy1, Osamah M Belali2, Mushtaq A Ansar2, Naif O Alharbi2. 1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia hkorashy@ksu.edu.sa. 2. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: SUN inhibits TNBC MDA-MB231 cell proliferation through activation of FOXO3a expression. Copyright
BACKGROUND: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. MATERIALS AND METHODS: 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. RESULTS: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. CONCLUSION:SUN inhibits TNBC MDA-MB231 cell proliferation through activation of FOXO3a expression. Copyright
Authors: Ali Alhoshani; Fahad O Alatawi; Fawaz E Al-Anazi; Ibraheem M Attafi; Asad Zeidan; Abdelali Agouni; Heba M El Gamal; Licia S Shamoon; Sarah Khalaf; Hesham M Korashy Journal: Onco Targets Ther Date: 2020-12-31 Impact factor: 4.147