Oxidative Stress Mediated Cytotoxicity, Cell Cycle Arrest, and Apoptosis Induced by Rosa damascena in Human Cervical Cancer HeLa Cells

Abstract

Rosa damascena Mill (Damask rose), belonging to the Rosaceae family, is known for medicinal purposes in traditional medicine system. However, its anticancer activity has not been studied yet in detail. Herein, we aimed to investigate the cytotoxic effects of R. damascena hexane (RA-HE) and methanolic (RA-ME) extracts against human breast (MCF-7), lung epithelial (A-549), and cervical (HeLa) cancer cells. The RA-HE and RA-ME showed more potent cytotoxic effects against HeLa cells with an $\text{I}{\text{C}}_{50}$ of 819.6 and 198.4 μg/ml, respectively. Further, cytotoxic concentrations of most effective extract (RA-ME) were used to evaluate the mechanism of cytotoxicity involved in HeLa cells. A concentration-dependent induction of lipid peroxidation (LPO) and reduction of glutathione (GSH) in HeLa cells treated with 250-1000 μg/ml of RA-ME confirms the association of oxidative stress. We also detected a noteworthy increase in reactive oxygen species (ROS) production and a decline in mitochondrial membrane potential (MMP) level in RA-ME-exposed HeLa cells. Flow cytometric data showed a strong dose-response relationship in cell cycle analysis between subG1 phase in HeLa cells and RA-ME treatment. Similarly, a concentration-dependent increase was recorded with Annexin V assay in HeLa cells going to late apoptosis. In conclusion, our findings suggest that RA-ME-induced cytotoxicity and apoptosis in HeLa cells are mediated by oxidative stress.