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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 (TET) on Akt activation in A549 cells. The cells were treated with (A) various concentrations (0, 10, 20 and 30 µM) of TET for 24 h or (B) 30 µM of TET for indicated times (0, 2, 4, 8, 12 and 24 h).
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Figure 4: The effect of tetrandrine (TET) on Akt activation in A549 cells. The cells were treated with (A) various concentrations (0, 10, 20 and 30 µM) of TET for 24 h or (B) 30 µM of TET for indicated times (0, 2, 4, 8, 12 and 24 h).

Mentions: Since Akt is a crucial mediator of carcinogenesis and the phosphorylation of Akt is essential for its full activity and is involved in apoptosis [9], we have measured the potential effects of TET on Akt phosphorylation. TET treatment suppressed Akt phosphorylation at both Thr308 and Ser473 in both time- and concentration-dependent manners, while the total Akt levels remained unchanged (Fig. 4). ERK is also known to be a pivotal factor in carcinogenesis and is closely associated with Akt signaling [19] and therefore the potential effects of TET treatment on ERK signaling were measured. Interestingly, TET also suppressed ERK phosphorylation in both time-/concentration- dependent manners similar to Akt phosphorylation (Fig. 5).


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 (TET) on Akt activation in A549 cells. The cells were treated with (A) various concentrations (0, 10, 20 and 30 µM) of TET for 24 h or (B) 30 µM of TET for indicated times (0, 2, 4, 8, 12 and 24 h).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: The effect of tetrandrine (TET) on Akt activation in A549 cells. The cells were treated with (A) various concentrations (0, 10, 20 and 30 µM) of TET for 24 h or (B) 30 µM of TET for indicated times (0, 2, 4, 8, 12 and 24 h).
Mentions: Since Akt is a crucial mediator of carcinogenesis and the phosphorylation of Akt is essential for its full activity and is involved in apoptosis [9], we have measured the potential effects of TET on Akt phosphorylation. TET treatment suppressed Akt phosphorylation at both Thr308 and Ser473 in both time- and concentration-dependent manners, while the total Akt levels remained unchanged (Fig. 4). ERK is also known to be a pivotal factor in carcinogenesis and is closely associated with Akt signaling [19] and therefore the potential effects of TET treatment on ERK signaling were measured. Interestingly, TET also suppressed ERK phosphorylation in both time-/concentration- dependent manners similar to Akt phosphorylation (Fig. 5).

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