Oncotarget

Research Papers:

Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/β-catenin signaling and epithelial-to-mesenchymal transition

Shan Deng _, Chris Kong Chu Wong, Hung-Cheng Lai and Alice Sze Tsai Wong

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:25897-25914. https://doi.org/10.18632/oncotarget.13071

Metrics: PDF 1400 views  |   HTML 1444 views  |   ?  


Abstract

Shan Deng1, Chris Kong Chu Wong2, Hung-Cheng Lai3, Alice Sze Tsai Wong1

1School of Biological Sciences, University of Hong Kong, Hong Kong

2Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong

3Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

Correspondence to:

Alice Sze Tsai Wong, email: awong1@hku.hk

Keywords: Wnt/β-catenin signaling, ovarian cancer, chemoresistance, cancer stem cells, ginsenoside

Received: January 28, 2016    Accepted: October 10, 2016    Published: November 04, 2016

ABSTRACT

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth. Rb1 and compound K treatment also sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These effects were associated with the Wnt/β-catenin signaling pathway by downregulating β-catenin/T-cell factor-dependent transcription and expression of its target genes ATP-binding cassette G2 and P-glycoprotein. We also identified reversal of epithelial-to-mesenchymal transition as a new player in the Rb1 and compound K-mediated inhibition of CSCs. Rb1 and compound K treatment also inhibited the self-renewal of CSCs derived from ovarian carcinoma patients as well as in xenograft tumor model. Moreover, we did not observe toxicity in response to doses of Rb1 and compound K that produced an anti-CSC effect. Therefore, Rb1 should be explored further as a promising nutraceutical prototype of treating refractory tumors.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 13071