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International audience; Cucurbitacin E (Cuc E), highly oxygenated triterpene from cucurbitaceae ă family, was demonstrated to possess anti-proliferative, ă anti-inflammatory and anti-oxidant activities. Here, we studied the ă effect of Cuc E on the properties of the phospholipid membrane. Large ă unilamellar vesicles, with and without sulforhodamine B (SRB), were ă prepared in the absence and presence of Cuc E. The fluorescence ă increase, resulting from SRB release from vesicles due to inhibition of ă auto-quenching, was used to assess the permeability of liposome at 4 ă degrees and 37 degrees C. At 4 degrees C, blank liposomes and those ă containing Cuc E were stable; while at 37 degrees C Cuc E loaded ă liposomes showed less stability than blank ones. The loading efficiency ă of Cuc E into the vesicles was demonstrated to be 85% by HPLC. Dynamic ă light scattering measurements showed that liposomes embedding Cuc E were ă smaller than those which did not. Multilamellar vesicles were ă manufactured from dipalmitoylphosphatidylcholine in the presence and ă absence of Cuc E (molar ratio 7%). Results obtained by differential ă scanning calorimetry suggest that Cuc E binds mainly at the polar/apolar ă interfacial region of lipid bilayers and may incorporate into the lipid ă bilayer. Cuc E does not produce phase separation and thus might be ă included in liposome formulation. (C) 2013 Elsevier B.V. All rights ă reserved.

International audience; 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.