1.Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.
Hyun Sun CHO ; Seung Hee CHANG ; Youn Sun CHUNG ; Ji Young SHIN ; Sung Jin PARK ; Eun Sun LEE ; Soon Kyung HWANG ; Jung Taek KWON ; Arash Minai TEHRANI ; Minah WOO ; Mi Sook NOH ; Huda HANIFAH ; Hua JIN ; Cheng Xiong XU ; Myung Haing CHO
Journal of Veterinary Science 2009;10(1):23-28
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.
Antineoplastic Agents, Phytogenic/*pharmacology
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Apoptosis/drug effects
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Benzylisoquinolines/*pharmacology
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Carcinoma/*drug therapy
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Extracellular Signal-Regulated MAP Kinases/*antagonists & inhibitors
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Humans
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Lung Neoplasms/*drug therapy
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