Isoreserpine promotes β-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells

Jungsug Gwak; Taeyun Song; Jie Young Song; Yeon Sook Yun; Il Whan Choi; Yongsu Jeong; Jae Gook Shin; Sangtaek Oh

doi:10.1016/j.bbrc.2009.07.027

Isoreserpine promotes β-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells

Jungsug Gwak, Taeyun Song, Jie Young Song, Yeon Sook Yun, Il Whan Choi, Yongsu Jeong, Jae Gook Shin, Sangtaek Oh

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

Aberrant accumulation of intracellular β-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular β-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, which was stimulated by Wnt3a-conditioned medium. We found that isoreserpine promoted the degradation of intracellular β-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells. Moreover, isoreserpine repressed the expression of β-catenin/T-cell factor (TCF)-dependent genes, such as cyclin D1 and c-myc, resulting in the suppression of HCT116 cell proliferation. Our findings suggest that isoreserpine can potentially be used as a chemotherapeutic agent against colon cancer.

Original language	English
Pages (from-to)	444-449
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	387
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2009.07.027
Publication status	Published - 25 Sept 2009

Bibliographical note

Funding Information:
We thank Y. Yang for ΔSiah-1 expression plasmid and M. Davis for dominant-negative β-TrCP expression plasmid. This work was supported by the Korea Institute of Science & Technology Evaluation and Planning (KISTEP) and Ministry of Science & Technology (MOST), Korean Government, through its National Nuclear Technology Program and by the Korea Science and Engineering Foundation (KOSEF) through the Medical Research Center Program funded by the Ministry of Science and Technology (R13-2007-023-00000-0).

Keywords

Colon cancer
Isoreserpine
Protein degradation
Siah-1
Wnt/β-catenin pathway
β-Catenin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2009.07.027

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title = "Isoreserpine promotes β-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells",

abstract = "Aberrant accumulation of intracellular β-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular β-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, which was stimulated by Wnt3a-conditioned medium. We found that isoreserpine promoted the degradation of intracellular β-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells. Moreover, isoreserpine repressed the expression of β-catenin/T-cell factor (TCF)-dependent genes, such as cyclin D1 and c-myc, resulting in the suppression of HCT116 cell proliferation. Our findings suggest that isoreserpine can potentially be used as a chemotherapeutic agent against colon cancer.",

keywords = "Colon cancer, Isoreserpine, Protein degradation, Siah-1, Wnt/β-catenin pathway, β-Catenin",

author = "Jungsug Gwak and Taeyun Song and Song, {Jie Young} and Yun, {Yeon Sook} and Choi, {Il Whan} and Yongsu Jeong and Shin, {Jae Gook} and Sangtaek Oh",

note = "Funding Information: We thank Y. Yang for ΔSiah-1 expression plasmid and M. Davis for dominant-negative β-TrCP expression plasmid. This work was supported by the Korea Institute of Science & Technology Evaluation and Planning (KISTEP) and Ministry of Science & Technology (MOST), Korean Government, through its National Nuclear Technology Program and by the Korea Science and Engineering Foundation (KOSEF) through the Medical Research Center Program funded by the Ministry of Science and Technology (R13-2007-023-00000-0).",

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AU - Song, Taeyun

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AU - Choi, Il Whan

AU - Jeong, Yongsu

AU - Shin, Jae Gook

AU - Oh, Sangtaek

N1 - Funding Information: We thank Y. Yang for ΔSiah-1 expression plasmid and M. Davis for dominant-negative β-TrCP expression plasmid. This work was supported by the Korea Institute of Science & Technology Evaluation and Planning (KISTEP) and Ministry of Science & Technology (MOST), Korean Government, through its National Nuclear Technology Program and by the Korea Science and Engineering Foundation (KOSEF) through the Medical Research Center Program funded by the Ministry of Science and Technology (R13-2007-023-00000-0).

PY - 2009/9/25

Y1 - 2009/9/25

N2 - Aberrant accumulation of intracellular β-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular β-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, which was stimulated by Wnt3a-conditioned medium. We found that isoreserpine promoted the degradation of intracellular β-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells. Moreover, isoreserpine repressed the expression of β-catenin/T-cell factor (TCF)-dependent genes, such as cyclin D1 and c-myc, resulting in the suppression of HCT116 cell proliferation. Our findings suggest that isoreserpine can potentially be used as a chemotherapeutic agent against colon cancer.

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KW - Isoreserpine

KW - Protein degradation

KW - Siah-1

KW - Wnt/β-catenin pathway

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Isoreserpine promotes β-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells

Abstract

Bibliographical note

Keywords

UN SDGs

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