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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 350239, 10 pages
http://dx.doi.org/10.1155/2012/350239
Research Article

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

1Department of Obstetrics and Gynecology, Tri-Service General Hospital, No. 325, Section 2, Cheng-Kung Road, Neihu, Taipei 11490, Taiwan
2School of Dentistry, National Defense Medical Center, No. 161, Section 6, Minquan E. Road, Neihu, Taipei 11490, Taiwan
3Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei 11490, Taiwan
4Kang-Ning Junior College of Medical Care and Management, Taipei 11490, Taiwan
5Department of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan
6Department of Pharmacology, National Defense Medical Center, Taipei 11490, Taiwan
7Department of Pathology, Da-Chien General Hospital, Miaoli 36052, Taiwan
8Department of Nursing, Jente Junior College of Medicine, Nursing, and Management, Miaoli 35664, Taiwan

Received 29 September 2012; Revised 28 November 2012; Accepted 2 December 2012

Academic Editor: Yoshiyuki Kimura

Copyright © 2012 Chien-Chih Ou et al. 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.

Abstract

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.