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.

Insights into Common Octopus (Octopus vulgaris) Ink Proteome and Bioactive Peptides Using Proteomic Approaches

“…Some of the previous studies reported that cephalopod ink extracts possess antimicrobial properties against diverse pathogenic bacteria [1,91]. Additionally, recently, it was found that O. vulgaris ink extracts exhibit anti-inflammatory, antiproliferative, antimutagenic, antioxidant, and cytoprotective properties [11,12]. There is currently no information concerning cephalopod ink bioactive peptides, but Nadarajah et al mentioned that fractions of melanin-free ink with low molecular weights (<3 kDa) showed the highest antioxidative activities [92].…”

“…The processing of squids, cuttlefish, and octopus generates large amounts of solid and liquid wastes in the forms of skin, head, cuttlebone, pen, ink, and viscera [10]. However, octopus ink by-products have received much attention due to the discovery of several relevant bioactive compounds [1, [10][11][12].…”

The Southern European Atlantic Diet and Its Supplements: The Chemical Bases of Its Anticancer Properties

“…This novel metabolite derived from Octopus vulgaris ink demonstrates proapoptotic effects on A549 lung cancer cells and inhibits pro-inflammatory markers [87]. Specifically, antiproliferative activity has been also observed in cell lines of certain cancer types such as prostate (22Rv1), lung (A549), and cervical epithelioid adenocarcinoma (HeLa) [88]. Additionally, Octopus vulgaris extracts containing OPC have shown anti-inflammatory activity in LPS-stimulated RAW 264.7 cells, highlighting the potential of Octopus vulgaris ink as a nutraceutical product or supplement with antitumoral action [87].…”

Recent Updates on Marine Cancer-Preventive Compounds

“…Burgos Hernández et al suggest that the fractionated hexane and methanol extract of octopus Paraoctopus limaculatus contained molecules capable of a chemoprotective activity [119,120]. A chemical analysis of the extract revealed the presence of compounds containing double bonds as well as oxygenated molecules (alcohols, ketones, and ethers).…”

“…The authors have made this speculation based on itsantimutagenic activity, which was detected in the bacterium-based assay with aflatoxin B1 as a mutagen. Additionally, an antiproliferative activity in murine B-cell lymphoma cells and an antioxidant activity in cell-free assay have been reported [119,120]. However, such speculationed chemoprotective properties require further experimental confirmation as no relevant assay in mammalian cells has been performed.…”