Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB

Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- an...

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Main Authors:	Ou, Chien-Chih, Chen, Yuan-Wu, Hsu, Shih-Chung, Sytwu, Huey-Kang, Loh, Shih-Hurng, Li, Jhy-Wei, Liu, Jah-Yao
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543825/

id	pubmed-3543825
recordtype	oai_dc
spelling	pubmed-35438252013-01-23 Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB Ou, Chien-Chih Chen, Yuan-Wu Hsu, Shih-Chung Sytwu, Huey-Kang Loh, Shih-Hurng Li, Jhy-Wei Liu, Jah-Yao Research Article Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between −207 and −103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent. Hindawi Publishing Corporation 2012 2012-12-24 /pmc/articles/PMC3543825/ /pubmed/23346199 http://dx.doi.org/10.1155/2012/350239 Text en Copyright © 2012 Chien-Chih Ou 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ou, Chien-Chih Chen, Yuan-Wu Hsu, Shih-Chung Sytwu, Huey-Kang Loh, Shih-Hurng Li, Jhy-Wei Liu, Jah-Yao
spellingShingle	Ou, Chien-Chih Chen, Yuan-Wu Hsu, Shih-Chung Sytwu, Huey-Kang Loh, Shih-Hurng Li, Jhy-Wei Liu, Jah-Yao Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB
author_facet	Ou, Chien-Chih Chen, Yuan-Wu Hsu, Shih-Chung Sytwu, Huey-Kang Loh, Shih-Hurng Li, Jhy-Wei Liu, Jah-Yao
author_sort	Ou, Chien-Chih
title	Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB
title_short	Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB
title_full	Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB
title_fullStr	Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB
title_full_unstemmed	Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB
title_sort	triptolide transcriptionally represses her2 in ovarian cancer cells by targeting nf-κb
description	Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between −207 and −103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent.
publisher	Hindawi Publishing Corporation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543825/
_version_	1611946596469047296

Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB

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