Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/ß-catenin signaling and epithelial-to-mesenchymal transition.
Oncotarget
; 8(16): 25897-25914, 2017 Apr 18.
Article
en En
| MEDLINE
| ID: mdl-27825116
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/ß-catenin signaling pathway by downregulating ß-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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
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Resistencia a Antineoplásicos
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Ginsenósidos
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Transición Epitelial-Mesenquimal
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Vía de Señalización Wnt
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Oncotarget
Año:
2017
Tipo del documento:
Article
País de afiliación:
Hong Kong