Cytotoxic effect of Drimia maritima bulb extract and induction of mitochondrial apoptotic signaling in human breast cancer cells, MCF-7 and MDA-MB-468

Abstract

Maryam Hamzeloo-Moghadam,1 Mahmoud Aghaei,2 Mohammad Hossein Abdolmohammadi,3 Amir Khalaj,1,4 Faranak Fallahian3 1Traditional Medicine and Materia Medica Research Center and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; 3Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran; 4Food and Drug Laboratory Research Center, Food and Drug Organization, Ministry of Health and Medical Education, Tehran, Iran Background: Drimia maritima (D. maritima) is a plant belonging to the family Asparagaceae, which has been used for the treatment of several ailments including cancer around the world. To our knowledge, there is no comprehensive study about the molecular mechanisms of anticancer activity of this plant, yet.Materials and methods: In the current study, cell viability, apoptosis induction, ROS production, mitochondrial apoptotic pathway, and ER stress mediators have been evaluated in breast cancer cells, MCF7, and MDA-MB-468 treated with D. maritima.Results: Significant cytotoxic effects were observed in MCF-7 and MDA-MB-468 cells after exposure to D. maritima. Apoptosis induction was determined using Annexin-V-FITC and propidium iodide staining. Furthermore, an increase of ROS, loss of mitochondrial membrane potential, the release of cytochrome c, activation of caspases, and elevation in the Bax/Bcl-2 ratio was determined. D. maritima dose-dependently increased the mRNA expression of ER stress markers such as CHOP, ATF-4, GADD34, and TRIB3 in MCF-7, and MDA-MB-468 cells.Conclusion: These data suggest that D. maritima induces apoptosis in human breast cancer cells via the mitochondrial-mediated pathway. In addition, endoplasmic reticulum stress seems to be involved in D. maritima-induced cell death. Keywords: Drimia maritima, ROS, apoptosis, mitochondria, breast cancer, ER stress&nbsp