The cucurbitacins E, D and I: Investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver

Abstract : Cucurbitacins are a class of natural compounds known for their numerous ă potential pharmacological effects. The purpose of this work was to ă compare the cytotoxicity of three cucurbitacins I, D, E on the ă chondrosarcoma SW 1353 cancer cell line and to investigate their ă biotransformation in man. Cucurbitacins I and D showed a very strong ă cytotoxicity, which was higher than that of cytochalasin D, used as a ă drug reference. Almost 100% of the cells were apoptotic as observed by ă DNA fragmentation (TUNEL assay) after 12 h with cucurbitacins I and D (1 ă mu M) and cucurbitacin E (10 mu M). In terms of IC50 values, ă cucurbitacins I and E presented a higher toxicity compared to that of ă cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by ă human hepatic microsomes, leading to cucurbitacin I (K-m 22 mu M, V-max ă 571 nmol/mg proteins/min). On the other hand, the three cucurbitacins ă were hydroxylated at a very low extent, but they were sulfated and ă glucuronidated. In terms of V-max/K-m, the cucurbitacin E was the best ă substrate of UDP-glucuronosyltransferases. This study shows that ă cucurbitacins I, D and E present a potent cytotoxic activity toward the ă chondrosarcoma SW 1353 cell line and are metabolized as sulfate and ă glucuronide conjugates. (C) 2012 Elsevier Ireland Ltd. All rights ă reserved.
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Toxicology Letters, Elsevier, 2013, 216 (2-3), pp.189-199. 〈10.1016/j.toxlet.2012.11.014〉
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Soumis le : vendredi 10 février 2017 - 13:23:34
Dernière modification le : vendredi 27 juillet 2018 - 11:06:03

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Suzanne Abbas, Jean-Baptiste Vincourt, Lamice Habib, Patrick Netter, Helene Greige-Gerges, et al.. The cucurbitacins E, D and I: Investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver. Toxicology Letters, Elsevier, 2013, 216 (2-3), pp.189-199. 〈10.1016/j.toxlet.2012.11.014〉. 〈hal-01464665〉

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