Marine Venoms and Marine-Derived Bioactive Compounds as Emerging Anticancer Agents: A Review of Cytotoxic and Apoptotic Mechanisms
Shiksha *
CAS in Marine Biology, Annamalai University, Parangipettai, Tamil Nadu -608502, India.
S. Bragadeeswaran
Marine Biotoxinology Lab., CAS in Marine Biology, Annamalai University, Parangipettai, Tamil Nadu – 608502, India.
*Author to whom correspondence should be addressed.
Abstract
The marine environment harbours an exceptional diversity of venomous and toxin-producing organisms whose secreted peptides, proteins and secondary metabolites have proved to be a rich and largely underexploited reservoir for oncological drug discovery. Cnidarians, cone snails, marine gastropods, scorpaeniform fishes and stingrays produce venoms containing pore-forming toxins, ion-channel modulators and protease-rich fractions that exert potent, often tumour-selective, cytotoxic effects, while sessile invertebrates such as sponges, tunicates and molluscs yield structurally distinctive alkaloids, nucleosides, macrolides and peptides that have already furnished several clinically approved chemotherapeutics. This narrative review synthesises the contemporary literature on the cytotoxic and apoptotic mechanisms of marine venoms and venom-derived compounds, alongside related marine natural products of non-venomous origin, with particular attention to membrane-disruptive cytotoxicity, ion-channel-mediated signalling, mitochondrial and death-receptor apoptotic cascades, and cell-cycle arrest. The pharmacology of established agents, including trabectedin, lurbinectedin, eribulin, cytarabine and the dolastatin-derived auristatins, is considered alongside emerging venom-derived candidates from sea anemones, jellyfish and venomous fishes, and the sulphated polysaccharide fucoidan from brown algae. Evidence for synergy with conventional chemotherapeutics, prospects for bioconjugation and targeted delivery, and the principal translational obstacles, including limited supply, structural complexity and unresolved pharmacokinetics, are discussed. The review concludes that marine venoms and venom-derived bioactive molecules represent a mechanistically diverse and clinically validated source of anticancer leads, but that systematic structural characterisation, standardised bioassay reporting and rational combination strategies will be required to translate this potential into new therapeutics.
Keywords: Marine venom, marine natural products, apoptosis, cytotoxicity, cnidarian toxin, conotoxin, fucoidan, trabectedin