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Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells

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 a...

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Autores principales: Cho, Sung-Yun, Lee, Hyo-Jeong, Lee, Hyo-Jung, Jung, Deok-Beom, Kim, Hyunseok, Sohn, Eun Jung, Kim, Bonglee, Jung, Ji Hoon, Kwon, Byoung-Mog, Kim, Sung-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622407/
https://www.ncbi.nlm.nih.gov/pubmed/23589723
http://dx.doi.org/10.1155/2013/974313
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author Cho, Sung-Yun
Lee, Hyo-Jeong
Lee, Hyo-Jung
Jung, Deok-Beom
Kim, Hyunseok
Sohn, Eun Jung
Kim, Bonglee
Jung, Ji Hoon
Kwon, Byoung-Mog
Kim, Sung-Hoon
author_facet Cho, Sung-Yun
Lee, Hyo-Jeong
Lee, Hyo-Jung
Jung, Deok-Beom
Kim, Hyunseok
Sohn, Eun Jung
Kim, Bonglee
Jung, Ji Hoon
Kwon, Byoung-Mog
Kim, Sung-Hoon
author_sort Cho, Sung-Yun
collection PubMed
description 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.
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spelling pubmed-36224072013-04-15 Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells Cho, Sung-Yun Lee, Hyo-Jeong Lee, Hyo-Jung Jung, Deok-Beom Kim, Hyunseok Sohn, Eun Jung Kim, Bonglee Jung, Ji Hoon Kwon, Byoung-Mog Kim, Sung-Hoon Evid Based Complement Alternat Med Research Article 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. Hindawi Publishing Corporation 2013 2013-03-26 /pmc/articles/PMC3622407/ /pubmed/23589723 http://dx.doi.org/10.1155/2013/974313 Text en Copyright © 2013 Sung-Yun Cho et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cho, Sung-Yun
Lee, Hyo-Jeong
Lee, Hyo-Jung
Jung, Deok-Beom
Kim, Hyunseok
Sohn, Eun Jung
Kim, Bonglee
Jung, Ji Hoon
Kwon, Byoung-Mog
Kim, Sung-Hoon
Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells
title Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells
title_full Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells
title_fullStr Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells
title_full_unstemmed Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells
title_short Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells
title_sort activation of amp-activated protein kinase α and extracelluar signal-regulated kinase mediates cb-pic-induced apoptosis in hypoxic sw620 colorectal cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622407/
https://www.ncbi.nlm.nih.gov/pubmed/23589723
http://dx.doi.org/10.1155/2013/974313
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