Cytotoxicity, Fractionation and Dereplication of Extracts of the Dinoflagellate Vulcanodinium rugosum, a Producer of Pinnatoxin G

Type Article
Date 2013-09
Language English
Author(s) Geiger Marie1, 2, Desanglois Gwenaelle3, Hogeveen Kevin3, Fessard Valerie3, Lepretre Thomas1, 2, Mondeguer FlorenceORCID1, Guitton Yann1, 2, Herve FabienneORCID1, Sechet VeroniqueORCID1, Grovel Olivier2, Pouchus Yves-Francois2, Hess PhilippORCID1
Affiliation(s) 1 : IFREMER, Ctr Atlantique, Lab Phycotoxines, F-44311 Nantes, France.
2 : Univ Nantes, LUNAM, Fac Pharm, MMS EA2160, F-44035 Nantes, France.
3 : ANSES, Unite Toxicol Contaminants, F-35302 Fougeres, France.
Source Marine Drugs (1660-3397) (Mdpi Ag), 2013-09 , Vol. 11 , N. 9 , P. 3350-3371
DOI 10.3390/md11093350
WOS© Times Cited 11
Keyword(s) dereplication, cyclic imine, HRMS, bioactivity, pinnatoxins
Abstract Pinnatoxin G (PnTX-G) is a marine toxin belonging to the class of cyclic imines and produced by the dinoflagellate Vulcanodinium rugosum. In spite of its strong toxicity to mice, leading to the classification of pinnatoxins into the class of “fast-acting toxins”, its hazard for human health has never been demonstrated. In this study, crude extracts of V. rugosum exhibited significant cytotoxicity against Neuro2A and KB cells. IC50 values of 0.38 µg mL−1 and 0.19 µg mL−1 were estimated on Neuro2A cells after only 24 h of incubation and on KB cells after 72 h of incubation, respectively. In the case of Caco-2 cells 48 h after exposure, the crude extract of V. rugosum induced cell cycle arrest accompanied by a dramatic increase in double strand DNA breaks, although only 40% cytotoxicity was observed at the highest concentration tested (5 µg mL−1). However, PnTX-G was not a potent cytotoxic compound as no reduction of the cell viability was observed on the different cell lines. Moreover, no effects on the cell cycle or DNA damage were observed following treatment of undifferentiated Caco-2 cells with PnTX-G. The crude extract of V. rugosum was thus partially purified using liquid-liquid partitioning and SPE clean-up. In vitro assays revealed strong activity of some fractions containing no PnTX-G. The crude extract and the most potent fraction were evaluated using full scan and tandem high resolution mass spectrometry. The dereplication revealed the presence of a major compound that could be putatively annotated as nakijiquinone A, N-carboxy-methyl-smenospongine or stachybotrin A, using the MarinLit™ database. Further investigations will be necessary to confirm the identity of the compounds responsible for the cytotoxicity and genotoxicity of the extracts of V. rugosum.
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Geiger Marie, Desanglois Gwenaelle, Hogeveen Kevin, Fessard Valerie, Lepretre Thomas, Mondeguer Florence, Guitton Yann, Herve Fabienne, Sechet Veronique, Grovel Olivier, Pouchus Yves-Francois, Hess Philipp (2013). Cytotoxicity, Fractionation and Dereplication of Extracts of the Dinoflagellate Vulcanodinium rugosum, a Producer of Pinnatoxin G. Marine Drugs, 11(9), 3350-3371. Publisher's official version : , Open Access version :