title: Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?
abstract: Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term "cytotoxicity" to be synonymous with "anticancer agent", which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.
authors.affiliation: ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. goncalomortagua@hotmail.com.|Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. goncalomortagua@hotmail.com.
authors.forename: Nelson G M
authors.initials: NG
authors.lastname: Gomes
authors.affiliation: Service de Neurochirurgie, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium. florence.lefranc@erasme.ulb.ac.be.
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.affiliation: ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. ankijjoa@icbas.up.pt.|Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. ankijjoa@icbas.up.pt.
authors.forename: Anake
authors.initials: A
authors.lastname: Kijjoa
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Campus de la Plaine, CP205/1, Boulevard du Triomphe, 1050 Brussels, Belgium. rkiss@ulb.ac.be.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059001:Aquatic Organisms / Q000382:microbiology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064210:Secondary Metabolism
chemical_list: D000970:Antineoplastic Agents
keywords: anticancer; chemotherapeutic; cytotoxic; in vivo antitumor; marine fungi; multidrug resistance; natural products; non-apoptotic; preclinical; pro-apoptotic