The herbal medicine sho-saiko-to inhibits the growth of malignant melanoma cells by upregulating Fas-mediated apoptosis and arresting cell cycle through downregulation of cyclin dependent kinases.
The anti-tumor effect and its mechanism of the herbal medicine sho-saiko-to were investigated on a murine malignant melanoma cell line (Mel-ret). Sho-saiko-to induced apoptotic cell death of Mel-ret cells with a definite increase of cell surface Fas antigen and Fas ligand (FasL). Sho-saiko-to arrested Mel-ret cells in G1 phase by decreasing the expression of cyclin-dependent kinase (cdk) 4 and its homologue cdk6. Kinase activities of cdk4 and cdk6 were identified to be downregulated by sho-saiko-to. Ingredient analysis revealed that baicalin is likely the main active constituent in the upregulation of Fas antigen and Fas ligand, while glycyrrhizin is the main constituent in the inhibition of cdks.
Liu
W
W
Department of Immunology, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Kato
M
M
Akhand
A A
AA
Hayakawa
A
A
Takemura
M
M
Yoshida
S
S
Suzuki
H
H
Nakashima
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D053222:Fas Ligand Protein; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008545:Melanoma / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008517:Phytotherapy; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; C018142:saiko-keishi-to; D018844:Cyclin-Dependent Kinases