Deguelin, an akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice

Hyoun Woo Kang, Jung Mogg Kim, Mi Yeon Cha, Hyun Chae Jung, In Sung Song, Joo Sung Kim

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers. Aims: This study was performed to elucidate the effect of deguelin on apoptotic pathways related to NF-κB signaling in colon cancer cells and on the anti-tumor effect in colon cancer xenograft mice. Methods: We studied COLO 205 and HCT116 cells in the presence or absence of deguelin. NF-κB signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for IjB phosphorylation/degradation, and by the electrophoretic mobility shift assay. Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. We also assessed the expression of antiapoptotic and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index was measured by the in vivo TUNEL assay. Results: Deguelin significantly inhibited IL-8 gene expression, IjB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells. Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-XL. In the colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher. Conclusion: Deguelin might be a potential therapeutic agent for treatment of colorectal cancer.

Original languageEnglish
Pages (from-to)2873-2882
Number of pages10
JournalDigestive Diseases and Sciences
Volume57
Issue number11
DOIs
StatePublished - 2012 Nov 1

Fingerprint

Colonic Neoplasms
Down-Regulation
Apoptosis
Growth
Neoplasms
Heterografts
Interleukin-8
Cell Death
Phosphorylation
deguelin
HCT116 Cells
Fluorescein-5-isothiocyanate
Annexin A5
In Situ Nick-End Labeling
Electrophoretic Mobility Shift Assay
Tumor Burden
Caspase 3
Real-Time Polymerase Chain Reaction
Colorectal Neoplasms
Western Blotting

Keywords

  • Apoptosis
  • Colon cancer
  • Deguelin
  • NF-κB

Cite this

Kang, Hyoun Woo ; Kim, Jung Mogg ; Cha, Mi Yeon ; Jung, Hyun Chae ; Song, In Sung ; Kim, Joo Sung. / Deguelin, an akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice. In: Digestive Diseases and Sciences. 2012 ; Vol. 57, No. 11. pp. 2873-2882.
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abstract = "Background: Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers. Aims: This study was performed to elucidate the effect of deguelin on apoptotic pathways related to NF-κB signaling in colon cancer cells and on the anti-tumor effect in colon cancer xenograft mice. Methods: We studied COLO 205 and HCT116 cells in the presence or absence of deguelin. NF-κB signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for IjB phosphorylation/degradation, and by the electrophoretic mobility shift assay. Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. We also assessed the expression of antiapoptotic and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index was measured by the in vivo TUNEL assay. Results: Deguelin significantly inhibited IL-8 gene expression, IjB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells. Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-XL. In the colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher. Conclusion: Deguelin might be a potential therapeutic agent for treatment of colorectal cancer.",
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Deguelin, an akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice. / Kang, Hyoun Woo; Kim, Jung Mogg; Cha, Mi Yeon; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung.

In: Digestive Diseases and Sciences, Vol. 57, No. 11, 01.11.2012, p. 2873-2882.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Deguelin, an akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice

AU - Kang, Hyoun Woo

AU - Kim, Jung Mogg

AU - Cha, Mi Yeon

AU - Jung, Hyun Chae

AU - Song, In Sung

AU - Kim, Joo Sung

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Background: Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers. Aims: This study was performed to elucidate the effect of deguelin on apoptotic pathways related to NF-κB signaling in colon cancer cells and on the anti-tumor effect in colon cancer xenograft mice. Methods: We studied COLO 205 and HCT116 cells in the presence or absence of deguelin. NF-κB signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for IjB phosphorylation/degradation, and by the electrophoretic mobility shift assay. Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. We also assessed the expression of antiapoptotic and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index was measured by the in vivo TUNEL assay. Results: Deguelin significantly inhibited IL-8 gene expression, IjB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells. Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-XL. In the colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher. Conclusion: Deguelin might be a potential therapeutic agent for treatment of colorectal cancer.

AB - Background: Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers. Aims: This study was performed to elucidate the effect of deguelin on apoptotic pathways related to NF-κB signaling in colon cancer cells and on the anti-tumor effect in colon cancer xenograft mice. Methods: We studied COLO 205 and HCT116 cells in the presence or absence of deguelin. NF-κB signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for IjB phosphorylation/degradation, and by the electrophoretic mobility shift assay. Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. We also assessed the expression of antiapoptotic and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index was measured by the in vivo TUNEL assay. Results: Deguelin significantly inhibited IL-8 gene expression, IjB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells. Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-XL. In the colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher. Conclusion: Deguelin might be a potential therapeutic agent for treatment of colorectal cancer.

KW - Apoptosis

KW - Colon cancer

KW - Deguelin

KW - NF-κB

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U2 - 10.1007/s10620-012-2237-x

DO - 10.1007/s10620-012-2237-x

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