title: Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells.
abstract: Tetrandrine, isolated from the root of Stephania tetrandra, has been used in Chinese medicine for the treatment of silicosis and arthritis, and it also has anti-tumor/growth activities. However, the signaling pathways of tetrandrine-induced growth arrest and apoptosis in cancer cells remain unclear. We investigated the molecular mechanisms of tetrandrine-induced apoptosis and growth arrest in human lung carcinoma cells. Upon treatment with tetrandrine, a time-dependent inhibition of cell growth was observed and cells developed many of the hallmark features of apoptosis. Flow cytometry analysis confirmed that tetrandrine increased populations of both apoptotic sub-G1 and G1 phase. Tetrandrine-induced growth inhibition was associated with induction of Cdk inhibitor p21, inhibition of cyclin D1 and activation of caspase-3. Tetrandrine also affected the expression patterns of cytoskeletons including distribution of F-actin and expression level of microtubule. These results suggest that tetrandrine merits further investigation as a cell cycle blocker as well as a cancer chemopreventive agent.
authors.affiliation: Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Research Institute of Oriental Medicine, Busan 614-052, Korea.
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Gyung Hwa
authors.initials: GH
authors.lastname: Kang
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Kim
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Park
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Kang
authors.forename: Yong Tae
authors.initials: YT
authors.lastname: Lee
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000199:Actins / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008870:Microtubules / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004365:Drugs, Chinese Herbal; D006131:Growth Inhibitors; D019938:Cyclin D1; C009438:tetrandrine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases