Antitumor activity and induction of apoptosis by water-soluble derivativesof 7 beta-hydroxycholesterol in human colon carcinoma cell lines

At present, cancer therapy of solid tumors, such as lung and colorectal can cer, is unsatisfactory. Recently, oxygenated sterols have shown selective c ytotoxicity against tumor cells. In this study, the cytotoxicity of 7 beta- hydroxycholesterol (7 beta HC) and two water-soluble derivatives of 7 beta HC, ie 7 beta HC-bis-hemisuccinate [disodium salt] (7 beta HC-HS) and 7 bet a HC-bis-hemisuccinate-diethanolaminoate (7 beta HC-EA), was determined in DLD-1, KM20L2, HCT-116, HT-29 and SW620 colon carcinoma cell lines using a cell count assay. IC50 values of the two water-soluble derivatives were, on the whole, comparable to 7 beta HC lying in the rang of 3-10 mu M. In addi tion, the water-soluble derivatives were able to induce apoptosis in the ex amined DLD-1 and KM20L2 colon carcinoma cell lines in contrast to the paren t compound 7 beta HC, as shown by DNA fragmentation, by the cleavage of DNA repair enzyme poly(ADP) ribose polymerase (PARP), and by the proteolytic c leavage of caspase-3 (CPP32). Due to the improved water-solubility of 7 bet a HC-HS and 7 beta HC-EA and their promising antitumor activity in vitro, a nimal studies in suitable tumor models are warranted.