The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis.
Solamargine, solasodine and khasianine steroidal alkaloids are utilized to determine the role of carbohydrate moiety in the mechanism of apoptosis. The C3 side chain of solamargine, khasianine and solasodine contains 4'Rha-Glc-Rha2', 4'Rha-Glc and H, respectively. Solamargine possessed potent cytotoxicity to human hepatoma cells, while the cytotoxicity of khasianine was greatly diminished. Nevertheless, only solamargine could induced "sub-G1" of apoptotic feature in flowcytometry. Thus, the 2'Rha moiety of solamargine may play a crucial role in triggering cell death by apoptosis. In addition, the molecular modeling of solamargine indicated that the 2'Rha moiety was adjacent to the rigid steroid structure, and drastically changed the dihedral angle of the glycosidic bond. The regulations of TNFR I and II expression by different carbohydrate moieties were also distinct. It implied that the carbohydrate moieties of steroidal alkaloids might alter the binding specificity to steroid receptors and consequently regulate the gene expression in different manners.
Chang
L C
LC
Department of Biochemistry, School of Pharmacy, Kaohsiung Medical College, Taiwan.
Tsai
T R
TR
Wang
J J
JJ
Lin
C N
CN
Kuo
K W
KW
D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008968:Molecular Conformation; D010840:Phytosterols / Q000737:chemistry / Q000633:toxicity*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012210:Rhamnose / Q000737:chemistry / Q000633:toxicity*; D012991:Solanaceous Alkaloids / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D010840:Phytosterols; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012991:Solanaceous Alkaloids; C110213:khasianine; C026609:beta-solamarine; C012037:solasodine; D012210:Rhamnose