Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds

10.1016/j.jtcme.2024.04.003

Shivbrat Upadhyay；Rumana Ahmad；Raushan Kumar；Sneha Ghildiyal；Alok Singh；Khursheed Ahmad；Ishrat Husain；Md. Abul Barkat；Mohd Zaheen Hassan；Yahya I. Asiri；Sahabjada Siddiqui

Allium sativum ； Anticancer ； HPLC analysis ； In silico analysis ； Triple-negative breast cancer

Journal of Traditional and Complementary Medicine

14卷6期（2024 / 11 / 01）

644 - 655

英文

Background and aim: Allium sativum L. has been used medicinally and traditionally since antiquity. This study sought to examine the Allium sativum ethanolic extract (ASEE) in inducing apoptosis in human triple-negative breast cancer (TNBC) MDA-MB-231 cells and the molecular interactions of the identified components with cell death markers using in silico method. Experimental procedure: Cytotoxicity of ASEE was tested on MCF-7, MDA-MB-231, and Normal Vero cells. The ROS production, apoptosis, MMP, and cell cycle study were conducted utilizing flow cytometer, and western blot was also performed for protein expression analysis. ASEE was phytochemically characterized by the HPLC while AutoDock Vina and iGEMDOCK tools investigated in-silico binding interactions. Results: The HPLC method identified two active organosulfur chemicals, allicin and alliin, in ASEE. MTT test revealed significant (p < 0.05) inhibition of breast cancer cells proliferation. The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells. TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP. ASEE exposure increased the percentage of cells in the G2/M phase. ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins. Allicin and alliin compounds had strong binding affinity with targeted proteins of breast cancer, and both compounds also showed good pharmacokinetics and druglikeness properties. Conclusion: ASEE could be useful in the treatment of human triple-negative breast cancer without any safety risks.