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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

Structure of alterporriol K (23) and L (24).
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marinedrugs-13-03950-f008: Structure of alterporriol K (23) and L (24).

Mentions: Dimeric anthraquinones known as alterporriols K (23) and L (24) (Figure 8) were reported from the endophytic fungus Alternaria sp. ZJ9-6N, which was isolated from the fruit of the marine mangrove Aegiceras corniculatum in Zhanjiang, Guangdong province, China [83]. Both 23 and 24 displayed modest cytotoxic activity against two human breast cancer cell lines (MDA-MB-435 and MCF-7) [83]. Further studies were performed to elucidate the molecular mechanisms underlying the alterporriol L (24) cytotoxic effect, showing that induced apoptosis and necrosis. As suggested by the increased levels of cytosolic free calcium and ROS production as well as the induced loss of MMPo in alterporriol L-treated MCF-7 cells, the apoptotic and necrotic effects are supposedly derived from the destruction of mitochondrial functions [84].


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

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

Structure of alterporriol K (23) and L (24).
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-03950-f008: Structure of alterporriol K (23) and L (24).
Mentions: Dimeric anthraquinones known as alterporriols K (23) and L (24) (Figure 8) were reported from the endophytic fungus Alternaria sp. ZJ9-6N, which was isolated from the fruit of the marine mangrove Aegiceras corniculatum in Zhanjiang, Guangdong province, China [83]. Both 23 and 24 displayed modest cytotoxic activity against two human breast cancer cell lines (MDA-MB-435 and MCF-7) [83]. Further studies were performed to elucidate the molecular mechanisms underlying the alterporriol L (24) cytotoxic effect, showing that induced apoptosis and necrosis. As suggested by the increased levels of cytosolic free calcium and ROS production as well as the induced loss of MMPo in alterporriol L-treated MCF-7 cells, the apoptotic and necrotic effects are supposedly derived from the destruction of mitochondrial functions [84].

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