Synthesis of the steroidal glycoside (25R)-3ß,16ß-diacetoxy-12,22-dioxo-5α-cholestan-26-yl ß-D-glucopyranoside and its anti-cancer properties on cervicouterine HeLa, CaSki, and ViBo cells.

ABSTRACT

The synthesis of the new glycoside (25R)-3ß,16ß-diacetoxy-12,22-dioxo-5α-cholestan-26-yl ß-D-glucopyranoside starting from hecogenin is described. This compound showed anti-cancer activity against cervicouterine cancer cells HeLa, CaSki and ViBo in the micromolar range. Its effect on cell proliferation, cell cycle and cell death is also described. The cytotoxic effect of the title compound on HeLa, CaSki and ViBo cells and human lymphocytes was evaluated through the LDH released in the culture supernatant, indicating that the main cell death process is not necrosis; the null effect on lymphocytes implies that it is not cytotoxic. The ability of this novel glycoside to induce apoptosis was investigated; several apoptosis events like chromatin condensation, formation of apoptotic bodies, as well as the increase in the expression of active caspase-3 and the fragmentation of DNA confirmed that the compound induced apoptosis in cervicouterine cancer cells. Significantly, the antiproliferative activity on tumor cells did not affect the proliferative potential of normal fibroblasts from cervix and peripheral blood lymphocytes. The glycoside showed selective antitumor activity and greater antiproliferative activity than its aglycon; it therefore serves as a promising lead candidate for further optimization.