The cucurbitacins E, D and I: investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver.
Fiche publication
Date publication
février 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAGDALOU Jacques, Dr VINCOURT Jean-Baptiste
Tous les auteurs :
Abbas S, Vincourt JB, Habib L, Netter P, Greige-Gerges H, Magdalou J
Lien Pubmed
Résumé
Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with cucurbitacins I and D (1 muM) and cucurbitacin E (10 muM). In terms of IC(50) values, cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (K(m) 22 muM, V(max) 571 nmol/mg proteins/min). On the other hand, the three cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of V(max)/K(m), the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.
Référence
Toxicol Lett. 2013 Feb 4;216(2-3):189-99