Ranking the cytotoxic potency of Ostreopsis cf. ovata, Ostreopsis cf. siamensis (O. sp. 9), and purified ovatoxins in human keratinocytes

Ovatoxins (OVTXs), a family of marine polyketides structurally similar to palytoxin (PLTX), are suspected to cause respiratory symptoms and skin irritation among coastal users during blooms of the dinoflagellate Ostreopsis cf. ovata . To investigate their role in cutaneous toxicity, crude extracts from six O. cf. ovata strains (OVTX(+) and OVTX(−)) and three O. cf. siamensis ( O . sp. 9) strains (OVTX(−)), along with six purified OVTX analogs, were tested for cytotoxicity (MTT assay) and cell death phenotypes (microscopy) in human keratinocyte models. Interestingly, cytotoxicity was driven by OVTX content, while OVTX(−) extracts were, on average, 150-fold and >1,000-fold less potent for O. cf. siamensis and O. cf. ovata , respectively. Nevertheless, the latter two induced PLTX-like cell death, suggesting the presence of unidentified PLTX-like toxins. Purified OVTXs exhibited sub-nanomolar cytotoxicity, 3.5- to 12.5-fold lower than PLTX (IC 50 = 0.036-0.642 nM vs. 0.011-0.049 nM), ranking in potency: PLTX > OVTX-d > OVTX-b > OVTX-a > OVTX-c > OVTX-e >>> OVTX-h (non-toxic, likely due to ring-opening). This study demonstrates the high toxic potency of OVTXs, close to that of PLTX, while providing a comprehensive cytotoxicity assessment of OVTX analogs, which could be useful for assessing the risks of human exposure.