title: Induction of G1 arrest and apoptosis in human cancer cells by crebanine, an alkaloid from Stephania venosa.
abstract: In this study, we focused the effects of crebanine, an alkaloid isolated from the tuber of Stephania venosa, on various human cancer cells. Crebanine treatment was found to significantly inhibit the proliferation of human leukemic cells (HL-60, U937 and K562), human fibrosarcoma cells (HT1080) and cervix cancer cell lines (KB-3-1 and KB-V1), of which HL-60 cells were the most sensitive to its treatment. In contrast, crebanine caused much less toxicity in human normal fibroblast cells. Our results demonstrated that crebanine mediated cell cycle arrest at G0/G1 phase and this was associated with down-regulation of cyclins A and D. In addition, crebanine induced apoptosis, which was detected by observation of the membrane phospholipid exposure in flow cytometry. Its induction of apoptosis was accompanied by an increase in cleavage of caspase-3, -8, -9 and poly(ADP-ribose) polymerase (PARP), and was attributable to the augmentation of Bax/Bcl proteins level. Crebanine also decreased mitochondrial membrane potential. Taken together, crebanine exerts anti-proliferative effects on human cancer cells through the induction of cell cycle arrest at the G1 phases and apoptosis. Our results suggest that crebanine is a promising new candidate as a chemotherapeutic agent for cancer therapy.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 53000, Thailand.
authors.forename: Pattama
authors.initials: P
authors.lastname: Wongsirisin
authors.forename: Supachai
authors.initials: S
authors.lastname: Yodkeeree
authors.forename: Wilart
authors.initials: W
authors.lastname: Pompimon
authors.forename: Pornngarm
authors.initials: P
authors.lastname: Limtrakul
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001060:Aporphines / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D031607:Stephania / Q000737:chemistry*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C061009:crebanine; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases