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Title 

Activation of AMP-activated protein kinase α and extracelluar signal-regulated kinase mediates CB-PIC-induced apoptosis in hypoxic SW620 colorectal cancer cells

Authors 

S Y ChoH J LeeHyo Jung LeeD B JungH KimE J SohnB KimJ H JungByoung-Mog KwonS H Kim

Publisher 

Hindawi Publishing Corporation

Issue Date 

2013

Citation 

Evidence-Based Complementary and Alternative Medicine, vol. 2013, no. 0, pp. 974313-974313

Abstract 

Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPKα blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPKα in hypoxic SW620 cells, implying cross-talk between ERK and AMPKα. Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1α and Akt/mTOR and the activation of AMPKα and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPKα in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPKα and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.

ISSN 

1741-427X

Link 

http://dx.doi.org/10.1155/2013/974313

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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