THE RHAMNOSE MOIETY OF SOLAMARGINE PLAYS A CRUCIAL ROLE IN TRIGGERINGCELL-DEATH BY APOPTOSIS

Solamargine, solasodine and khasianine steroidal alkaloids are utilize d to determine the role of carbohydrate moiety in the mechanism of apo ptosis. The CS side chain of solamargine, khasianine and solasodine co ntains 4'Rha-Glc-Rha2', 4'Rha-Glc and H, respectively. Solamargine pos sessed potent cytotoxicity to human hepatoma cells, while the cytotoxi city of khasianine was greatly diminished. Nevertheless, only solamarg ine could induce ''sub-G1'' of apoptotic feature in flowcytometry. Thu s, the 2'Rha moiety of solamargine may play a crucial role in triggeri ng cell death by apoptosis. In addition, the molecular modeling of sol amargine indicated that the 2'Rha moiety was adjacent to the rigid ste roid structure, and drastically changed the dihedral angle of the glyc osidic bond. The regulations of TNFR I and II expression by different carbohydrate moieties were also distinct. It implied that the carbohyd rate moieties of steroidal alkaloids might alter the binding specifici ty to steroid receptors and consequently regulate the gene expression in different manners. (C) 1998 Academic Press.