Unveiling the anticancer potential of Anamirta cocculus (L.) Wight& Arn.: Evidences from cytotoxicity studies, apoptosis analysis, and molecular docking.

Anamirta cocculus, a woody climber, is extensively utilised in traditional Asian medicine. This study investigates the cytotoxic effects of A. cocculus leaf extracts on various cancer cell lines as well as on a normal cell line. The ethyl acetate extract exhibited potent anticancer activity, with the highest cytotoxicity observed against ovarian cancer cell line (PA1) (IC₅₀ = 8.30 ± 0.38 µg/mL) and colorectal adenocarcinoma cell line (HT29) (IC₅₀ = 17.97 ± 0.63 µg/mL). Notably, the extract displayed low toxicity (18.72 ± 0.73%) on the normal human keratinocyte cell line (HaCaT) at a concentration of 100 µg/mL, indicating selective cytotoxicity towards cancer cells. The acetone extract also demonstrated significant cytotoxicity against various cancer cell lines, including A498, MG63, PA1, and UM-SCC-83B. The ethyl acetate extract of A. cocculus demonstrated potent inhibition of colony formation in HT29 and PA1 cancer cell lines while inducing apoptosis, as evidenced by membrane blebbing, chromatin condensation, and DNA fragmentation. The number of late apoptotic cells increased with an increase in concentrations of ACLE. Molecular docking studies of compounds identified through GC-MS analysis revealed strong interactions with key apoptotic proteins, including caspase-8, p53, caspase-3, and caspase-9. Compounds such as vitamin E, epoxylathyrol, squalene, and phytol showed high binding affinity to these proteins, suggesting their role in apoptosis induction. The possibility of induction of apoptotic proteins through indirect interaction by binding to other proteins or receptors cannot be ruled out. The cytotoxic effects may result from individual, combined, or synergistic actions of these compounds. Among these, epoxylathyrol emerged as a particularly promising anticancer drug candidate based on ADME analysis and binding affinity assessments, warranting further investigation.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04096-2.