Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells.
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.
Lee
Jun Hyuk
JH
Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Research Institute of Oriental Medicine, Busan 614-052, Korea.
Kang
Gyung Hwa
GH
Kim
Kyung Chul
KC
Kim
Kyoung Mi
KM
Park
Dong Il
DI
Choi
Byung Tae
BT
Kang
Ho Sung
HS
Lee
Yong Tae
YT
Choi
Yung Hyun
YH
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
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