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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 hirsutanol A (67).
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marinedrugs-13-03950-f027: Structure of hirsutanol A (67).

Mentions: Hirsutanol A (67) (Figure 27), a hirsutane-based sesquiterpene, was first reported in the salt water culture of an unidentified marine sponge-associated fungus (95-1005C) [152]. Hirsutanol A (67), as well as other derivatives of this class of sesquiterpenes, was later isolated from the EtOAc extract of a culture of the fungus Chondrostereum sp. SF002, which was isolated from the soft coral Sarcophyton tortuosum that was collected from Sanya Bay in the southern China Sea [153,154]. Hirsutanol A (67) was found to inhibit cell proliferation, elevate the ROS level, and induce apoptosis and autophagy in MCF-7 human breast cancer cells [155]. It therefore seems that hirsutanol A (67) could induce apoptosis and autophagy via the accumulation of ROS, and co-treatment with an autophagy inhibitor was able to sensitize MCF-7 cells to hirsutanol A (67) [155]. Hirsutanol A (67) also activates the JNK signaling pathway by elevating the ROS level [156]. In contrast with other hirsutane sesquiterpenoids, which lack the α-methylidene oxo group, hirsutanol A (67) displayed a potent cytotoxicity against 15 distinct human cancer cell lines [153]. These results indicated that the α-methylidene oxo group is required for the cytotoxic activity of this class of sesquiterpenoids, possibly by enzymatic inactivation via alkylation [153].


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

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

Structure of hirsutanol A (67).
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-03950-f027: Structure of hirsutanol A (67).
Mentions: Hirsutanol A (67) (Figure 27), a hirsutane-based sesquiterpene, was first reported in the salt water culture of an unidentified marine sponge-associated fungus (95-1005C) [152]. Hirsutanol A (67), as well as other derivatives of this class of sesquiterpenes, was later isolated from the EtOAc extract of a culture of the fungus Chondrostereum sp. SF002, which was isolated from the soft coral Sarcophyton tortuosum that was collected from Sanya Bay in the southern China Sea [153,154]. Hirsutanol A (67) was found to inhibit cell proliferation, elevate the ROS level, and induce apoptosis and autophagy in MCF-7 human breast cancer cells [155]. It therefore seems that hirsutanol A (67) could induce apoptosis and autophagy via the accumulation of ROS, and co-treatment with an autophagy inhibitor was able to sensitize MCF-7 cells to hirsutanol A (67) [155]. Hirsutanol A (67) also activates the JNK signaling pathway by elevating the ROS level [156]. In contrast with other hirsutane sesquiterpenoids, which lack the α-methylidene oxo group, hirsutanol A (67) displayed a potent cytotoxicity against 15 distinct human cancer cell lines [153]. These results indicated that the α-methylidene oxo group is required for the cytotoxic activity of this class of sesquiterpenoids, possibly by enzymatic inactivation via alkylation [153].

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