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

Abstract

BackgroundVenoms 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.MethodsThe 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.ResultsD. 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.ConclusionsDasyatis sephen venom exhibits potent antiproliferative effect on HeLa cell line and upon further purification it could be a promising antiproliferative agent.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-015-0036-5) contains supplementary material, which is available to authorized users.

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

“…Through this dye, the main results confirmed that both Bothrops venoms decreased mitochondrial membrane potential when compared to untreated cells. Our results were similar to the findings of Rajeshkumar et al [36] who found that the marine animal venom Dasyatis sephen depolarized the mitochondrion of HeLa cell.…”

Stingray Venom Proteins: Mechanisms of Action Revealed Using a Novel Network Pharmacology Approach

“…Although the precise MoAs remain unknown, the translocation of Nf-κB, mitochondrial impairment, and the disruption of the ER and lysosomes indicate oxidative stress at the cellular level [44]. The mitochondrial signal in particular matches previous finding that venom of the marine stingray Pastinachus (Dasyatis) sephen alters mitochondrial membrane potential by enhancing the production of reactive oxygen species [45]. In the ER and lysosome, swelling, loss of membrane integrity, and even toxin accumulation can contribute to the observed effects [44,[46][47][48].…”

Effects of astaxanthin on oxidative stress induced by Cu2+ in prostate cells

“…Intracellular ROS levels were measured using the cell permeable substrate 2',7'-dichlorofluorescein diacetate (DCFH-DA), a converted detectable fluorescent product (Rajeshkumar et al, 2015). After 48 h incubation, the cells were washed with a cold PBS solution prior to adding 1 ml PBS containing 10 μmol/L DCFH-DA (excitation: 488 nm; emission: 525 nm), and then continually incubated for 20 min in the dark at 37 °C.…”