Saade Abdalkareem Jasim - Medical Laboratory Techniques Department, Al-Maarif University College, Al-anbar-Ramadi, Iraq
Omer Zedan Khalaf - Al-Anbar Health Directorate, Iraq
Shadia Hamoud Alshahrani - Medical Surgical Nursing Department, King Khalid University, Almahala, Abha, Saudi Arabia
Kadda Hachem - Laboratory of Biotoxicology, Pharmacognosy and Biological Valorization of Plants (LBPVBP), Faculty of Sciences, University of Saida-Dr Moulay Tahar, ۲۰۰۰۰ Saida, Algeria
Shukhrat Ziyadullaev - Department of Internal Diseases, Vice-rector for Scientific Affairs and Innovations, Samarkand State Medical University, Amir Temur Street ۱۸, Samarkand, Uzbekistan
Abduladheem Turki Jalil - Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, ۵۱۰۰۱, Iraq
ChangMing Wang - International College, Krirk University, Bangkok, ۳ Ram Inthra Rd, Khwaeng Anusawari, Khet Bang Khen, Krung Thep Maha Nakhon, ۱۰۲۲۰, Thailand
Rahman S. Zabibah - Medical Laboratory Technology Department, College of Medical Technology, Islamic University, Najaf, Iraq
Yousef A. Bin Jardan - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Qutaiba A. Qasim - College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq
Marwah Suliman Maashi - Medical Laboratory Science Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah ۲۱۵۸۹, Saudi Arabia
Yasser Fakri Mustafa - Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul-۴۱۰۰۱, Iraq

Objective(s): Breast cancer is the most prevalent cancer among females with different molecular subtypes. Corosolic acid is a pentacyclic triterpenoid with anti-cancer properties. Materials and Methods: The MTT assay was used to assess the cytotoxic activity of corosolic acid on MDA-MB-۲۳۱ and MCF۷ cell lines. To determine the apoptotic cells, the flow cytometry technique was utilized. The expression levels of apoptosis-related genes and proteins were quantified using quantitative real time-PCR (qRT-PCR) and Western blotting methods. The activity of caspase enzymes was measured by spectrophotometry.  Results: Corosolic acid significantly inhibited the proliferation of both cell lines compared with controls. This agent markedly induced apoptosis in MDA-MB-۲۳۱ cells but did not affect MCF۷ cells compared with controls. Treating the MADA-MB-۲۳۱ and MCF۷ cell lines with corosolic acid showed an inducing effect on apoptosis-associated caspases, including Caspase-۸, ۹, and -۳, in MADA-MB-۲۳۱ cells with no effect on apoptotic markers in MCF۷ cells. Further experiments uncovered corosolic acid-induced apoptosis in MADA-MB-۲۳۱ cells by decreasing the expression of the phosphorylated form of JAK۲ and STAT۳ proteins.Conclusion: The present data suggested that corosolic acid is an apoptosis-inducing phytochemical in triple-negative breast cancer MADA-MB-۲۳۱ cells. Also, corosolic acid triggered apoptosis in these cells by stimulating both pathways of apoptosis and inhibiting the JAK/STAT signaling. Furthermore, corosolic acid was found to inhibit MCF۷ cell proliferation by a non-apoptotic mechanism.

Apoptosis, Breast Cancer, Corosolic acid, JAK۲, STAT۳