Triptolide transcriptionally represses HER2 in ovarian cancer cells by targeting NF-κB

14Citations
Citations of this article
9Readers
Mendeley users who have this article in their library.

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- κ B. Previous reports demonstrated that TPL suppresses NF- κ B expression. We demonstrate that overexpression of NF- κ B 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.

Cite

CITATION STYLE

APA

Ou, C. C., Chen, Y. W., Hsu, S. C., Sytwu, H. K., Loh, S. H., Li, J. W., & Liu, J. Y. (2012). Triptolide transcriptionally represses HER2 in ovarian cancer cells by targeting NF-κB. Evidence-Based Complementary and Alternative Medicine, 2012. https://doi.org/10.1155/2012/350239

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free