Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.
Cho
Hyun Sun
HS
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
Chang
Seung Hee
SH
Chung
Youn Sun
YS
Shin
Ji Young
JY
Park
Sung Jin
SJ
Lee
Eun Sun
ES
Hwang
Soon Kyung
SK
Kwon
Jung Taek
JT
Tehrani
Arash Minai
AM
Woo
Minah
M
Noh
Mi Sook
MS
Hanifah
Huda
H
Jin
Hua
H
Xu
Cheng Xiong
CX
Cho
Myung Haing
MH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; C009438:tetrandrine; D048049:Extracellular Signal-Regulated MAP Kinases