Combined cytotoxicity of the phycotoxin okadaic acid and mycotoxins on intestinal and neuroblastoma human cell models
Hayashi, A and Dorantes-Aranda, JJ and Bowman, JP and Hallegraeff, G, Combined cytotoxicity of the phycotoxin okadaic acid and mycotoxins on intestinal and neuroblastoma human cell models, Toxins, 10, (12) Article 526. ISSN 2072-6651 (2018) [Refereed Article]
Mycotoxins are emerging toxins in the marine environment, which can co-occur with
algal toxins to exert synergistic or antagonistic effects for human seafood consumption. The current
study assesses the cytotoxicity of the algal toxin okadaic acid, shellfish, and dust storm-associated
mycotoxins alone or in combination on human intestinal (HT-29) and neuroblastoma (SH-SY5Y)
cell lines. Based on calculated IC50 (inhibitory concentration 50%) values, mycotoxins and the
algal toxin on their own exhibited increased cytotoxicity in the order of sydowinin A < sydowinin
B << patulin < alamethicin < sydowinol << gliotoxin = okadaic acid against the HT-29 cell line, and
sydowinin B < sydowinin A << alamethicin = sydowinol < patulin, << gliotoxin < okadaic acid
against the SH-SY5Y cell line. Combinations of okadaic acid–sydowinin A, –alamethicin, –patulin, and
–gliotoxin exhibited antagonistic effects at low-moderate cytotoxicity, but became synergistic at high
cytotoxicity, while okadaic acid–sydowinol displayed an antagonistic relationship against HT-29 cells.
Furthermore, only okadaic acid–sydowinin A showed synergism, while okadaic acid–sydowinol,
–alamethicin, –patulin, and –gliotoxin combinations demonstrated antagonism against SH-SY5Y.
While diarrhetic shellfish poisoning (DSP) from okadaic acid and analogues in many parts of the
world is considered to be a comparatively minor seafood toxin syndrome, our human cell model
studies suggest that synergisms with certain mycotoxins may aggravate human health impacts,
depending on the concentrations. These findings highlight the issues of the shortcomings of current
regulatory approaches, which do not regulate for mycotoxins in shellfish and treat seafood toxins as
if they occur as single toxins.