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Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.

Cho HS, Chang SH, Chung YS, Shin JY, Park SJ, Lee ES, Hwang SK, Kwon JT, Tehrani AM, Woo M, Noh MS, Hanifah H, Jin H, Xu CX, Cho MH - J. Vet. Sci. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.

ABSTRACT
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.

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The effect of tetrandrine on the proliferation of A549 cells. The viability of A549 cells was measured using the MTT assay. The cells were incubated with increasing concentrations of tetrandrine for (A) 24 h or (B) 48 h. Data are presented as mean ± SE of 3 independent experiments. *p < 0.05, **p < 0.01.
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Figure 1: The effect of tetrandrine on the proliferation of A549 cells. The viability of A549 cells was measured using the MTT assay. The cells were incubated with increasing concentrations of tetrandrine for (A) 24 h or (B) 48 h. Data are presented as mean ± SE of 3 independent experiments. *p < 0.05, **p < 0.01.

Mentions: To determine the effects of TET on cell viability, the MTT assay was performed on A549 cells treated with various concentrations of TET. The cells were exposed to 0-60 µM of TET for 24 h and 48 h. TET treatment significantly reduced the rate of cell proliferation compared to that of control cells in both time-/concentration-dependent manners. The reduction of cell proliferation and thus cell viability following treatment with 30 µM TET was roughly 59% at 24 h (Fig. 1A) and 43% at 48 h (Fig. 1B). These results led us to use 30 µM of TET for further studies.


Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells.

Cho HS, Chang SH, Chung YS, Shin JY, Park SJ, Lee ES, Hwang SK, Kwon JT, Tehrani AM, Woo M, Noh MS, Hanifah H, Jin H, Xu CX, Cho MH - J. Vet. Sci. (2009)

The effect of tetrandrine on the proliferation of A549 cells. The viability of A549 cells was measured using the MTT assay. The cells were incubated with increasing concentrations of tetrandrine for (A) 24 h or (B) 48 h. Data are presented as mean ± SE of 3 independent experiments. *p < 0.05, **p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801106&req=5

Figure 1: The effect of tetrandrine on the proliferation of A549 cells. The viability of A549 cells was measured using the MTT assay. The cells were incubated with increasing concentrations of tetrandrine for (A) 24 h or (B) 48 h. Data are presented as mean ± SE of 3 independent experiments. *p < 0.05, **p < 0.01.
Mentions: To determine the effects of TET on cell viability, the MTT assay was performed on A549 cells treated with various concentrations of TET. The cells were exposed to 0-60 µM of TET for 24 h and 48 h. TET treatment significantly reduced the rate of cell proliferation compared to that of control cells in both time-/concentration-dependent manners. The reduction of cell proliferation and thus cell viability following treatment with 30 µM TET was roughly 59% at 24 h (Fig. 1A) and 43% at 48 h (Fig. 1B). These results led us to use 30 µM of TET for further studies.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus