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, Alice Sze Tsai Wong

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumorinitiating 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.

Original languageEnglish
Pages (from-to)25897-25914
Number of pages18
JournalOncotarget
Volume8
Issue number16
DOIs
Publication statusPublished - 2017

Keywords

  • Cancer stem cells
  • Chemoresistance
  • Ginsenoside
  • Ovarian cancer
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Oncology

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