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Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

Gomes NG, Lefranc F, Kijjoa A, Kiss R - Mar Drugs (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. goncalomortagua@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

Structures of gliotoxin (7) and gliotoxin derivatives 8–9.
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marinedrugs-13-03950-f003: Structures of gliotoxin (7) and gliotoxin derivatives 8–9.

Mentions: Gliotoxin (7) (Figure 3), the first member of the epipolythiodiketopiperazine class and bridged diketopiperazine alkaloids, has been widely reported as constituent of several marine-derived fungi [52,53,54]. Recently, Nguyen et al. [55] reported the isolation and evaluation of the anticancer activity of gliotoxin (7) from Aspergillus sp. strain YL-06, which was isolated from a marine brown alga collected in Ulsan, Korea. This compound is pro-apoptotic in human HeLa cervix carcinoma and SW1353 chondrosarcoma cells through the activation of caspase-3, caspase-8 and caspase-9, the down-regulation of Bcl-2, the up-regulation of Bax and the release of cytochrome c (cyt c) [55].


Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

Gomes NG, Lefranc F, Kijjoa A, Kiss R - Mar Drugs (2015)

Structures of gliotoxin (7) and gliotoxin derivatives 8–9.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4483665&req=5

marinedrugs-13-03950-f003: Structures of gliotoxin (7) and gliotoxin derivatives 8–9.
Mentions: Gliotoxin (7) (Figure 3), the first member of the epipolythiodiketopiperazine class and bridged diketopiperazine alkaloids, has been widely reported as constituent of several marine-derived fungi [52,53,54]. Recently, Nguyen et al. [55] reported the isolation and evaluation of the anticancer activity of gliotoxin (7) from Aspergillus sp. strain YL-06, which was isolated from a marine brown alga collected in Ulsan, Korea. This compound is pro-apoptotic in human HeLa cervix carcinoma and SW1353 chondrosarcoma cells through the activation of caspase-3, caspase-8 and caspase-9, the down-regulation of Bcl-2, the up-regulation of Bax and the release of cytochrome c (cyt c) [55].

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. goncalomortagua@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus