Antiproliferative activity of marine stingray Dasyatis sephen venom on human cervical carcinoma cell line

RK Rajeshkumar, R Vennila, S Karthikeyan, N Rajendra Prasad, M Arumugam, T Velpandian, T Balasubramaniam

Venoms comprise mixtures of numerous bioactive compounds that have a wide range of pharmacologic actions. Toxins from venomous animals have attracted the attention of researchers because of their affinity for primary sites responsible for lethality and their efficacy at extremely low concentrations. The venoms of marine stingrays have not been extensively studied and limited data is available on them. The present study aims to evaluate the antiproliferative and biochemical properties of the venom obtained from a species of marine stingray (Dasyatis sephen) on human cervical cancer cell line HeLa. The antiproliferative effect of D. sephen venom was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation method along with assessment of changes in the enzymatic and non-enzymatic antioxidant status. We observed intracellular reactive oxygen species (ROS) levels by DCFH-DA method, mitochondrial membrane potential alterations by rhodamine 123 staining and apoptotic morphological changes by acridine orange/ethidium bromide dual staining method. D. sephen venom enhances lipid peroxidative markers such as thiobarbituric acid reactive substance, conjugated diene, and lipid hydroperoxide in HeLa cell lines. Stingray venom enhances the ROS levels, which is evidenced by the increased 2-7-diacetyl dichlorofluorescein fluorescence. Further, D. sephen venom treatment altered the mitochondrial membrane potential in HeLa cells. Additionally, we observed increased apoptotic morphological changes in D. sephen venom-treated groups. Dasyatis sephen venom exhibits potent antiproliferative effect on HeLa cell line and upon further purification it could be a promising antiproliferative agent.