KMID : 0893420090100010023
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Journal of Veterinary Science 2009 Volume.10 No. 1 p.23 ~ p.28
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Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells
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Cho Hyun-Sun
Hwang Soon-Kyung Chang Seung-Hee Tehrani Arash Minai Park Sung-Jin Cho Myung-Haing Woo Min-Ah Chang Youn-Sun Lee Eun-Sun Shin Ji-Young Kwon Jung-Taek Noh Mi-Sook Cheng Xiong Xu
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Abstract
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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-/concentrationdependent 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.
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KEYWORD
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A549 cells, Akt, apoptosis, Erk, tetrandrine
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