Octopus vulgaris ink extracts exhibit antioxidant, antimutagenic, cytoprotective, antiproliferative, and proapoptotic effects in selected human cancer cell lines

Abstract: Cancer is a noncommunicable disease of rising worldwide concern. Marine food products such as Octopus vulgaris ink (OI) could be sources of compounds addressing these concerns. This study aimed to evaluate the antimutagenic, cytoprotective, antiproliferative, proapoptotic, and antioxidant capacity of OI extracts on human cancer cell lines (22Rv1, HeLa, A549). The ARPE-19 cell line was used as a reference human cell line to evaluate the ink's cytotoxicity. The water extract exhibited the highest antimutagenic and cytoprotective effect, but the dichloromethane extract (DM) showed the lowest half lethal concentration against 22Rv1 cells. Structural elucidation of purified DM fractions (F1, F2, F3) identified an unreported compound, N-(2-ozoazepan-3-yl)-pyrrolidine-2-carboxamide (OPC). DM-F2 showed high antiproliferative effect (LC₅₀ = 27.6 µg/mL), reactive species modulation, early-apoptosis induction (42.9%), and nuclei disruption in 22Rv1 cells. In silico analysis predicted high OPC affinity with Cyclin D1 (−6.70 kcal/mol), suggesting its potential impact on cell cycle arrest. These results highlight the antimutagenic, cytoprotective, and antiproliferative potential health benefits derived from underutilized marine food products such as OI. Further investigations at in vitro or in vivo levels are required to elucidate mechanisms and health benefits from OI. Practical Application: O. vulgaris ink is an underutilized marine natural product that could be a source of biological compounds with potential health benefits such as antioxidant activity and cancer prevention.