Cytotoxicity and apoptosis induction of the marine Conus flavidus venom in HepG2 cancer cell line

Cancer is still an area of continuous research for finding more effective and selective agents, so our study aimed to explore new anticancer medicines from Cone snails' venoms as marine natural products with promising biological activities. Venoms from seven cone snails collected from two locations on the Red Sea coast (Marsa Alam (Ma) and Hurghada (Hu)) were extracted and subjected to SDS for protein concentrations. The venoms of C. vexillum (Ma), C. vexillum (Hu), and C. flavidus were found to have the highest protein concentrations (2.66, 2.618, and 2.611 mg/mL, respectively). The venom of C. vexillum (Ma) was found to be cytotoxic against the lung cancer cell line A549 (IC₅₀ = 4.511 ± 0.03 µg/mL). On the other hand, the venom of C. flavidus showed a strong cytotoxic effect on both liver and lung cancer cell lines (IC₅₀ = 1.593 ± 0.05 and 7.836 ± 0.4 µg/mL, respectively) when compared to their normal cell lines. Investigating the apoptotic cell death of C. flavidus venom on HepG2 cell lines, it showed total apoptotic cell death by 22.42-fold compared to untreated control and arresting the cell cycle at G2/M phase. Furthermore, its apoptotic cell death in HepG2 cells was confirmed through the upregulation of pro-apoptotic markers and down-regulation of Bcl-2 in both gene and protein expression levels. These findings confirmed the cytotoxic activity of C. flavidus venom through apoptotic cell death in HepG2 cells. So, a detailed study highlighting its structure and molecular target for developing new anticancer agents from natural sources is required.Communicated by Ramaswamy H. Sarma.