The cellular activity of cucurbitacin I is inhibited by glycosylation

Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the effects of cucurbitacin glucosides and their aglycone counterparts on the human epithelial carcinoma cell line (HeLa). Lipophilic or aqueous extracts were prepared from seeds of Citrullus colocynthis (Cucurbitaceae). Five types of cucurbitacin glucosides (E, I, L, J, K) and two aglycones (E, I) were then isolated by HPLC and the chemical structures were elucidated by their UV, NMR and mass spectrometry data. Cucurbitacins E and I were the most abundant compounds isolated from C. colocynthis. We found that, at nanomolar concentrations, the aglycones of cucurbitacines I and E lead to alterations in the morphology of HeLa cells, with the formation of sub-membrane inclusions. Several nuclei appeared in these cells after 24h of drug exposure suggesting that cucurbitacines E and I inhibit cytokinesis but not mitosis. They also cause changes in the distribution of F-actin but not in the microtubule network. In contrast to their aglycone forms, glucosylated cucurbitacins I and E, at the same nanomolar concentrations, do not have impact on HeLa cells. However, after 24h of treatment with cucurbitacin glucosides E and I, an aggregation of actin was observed at micromolar concentrations. The data suggest that the cell activities induced by the cucurbitacins studied result from the interaction of their aglycone forms with cell receptor(s) still to be discovered.

Keywords: Citrullus colocynthis, Cucurbitacin I, Cucurbitacin E