Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract

Dong,Ruochen; Chen,Ping; Chen,Qi

doi:10.3892/or.2018.6713

Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract

Authors:
- Ruochen Dong
- Ping Chen
- Qi Chen
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Affiliations: Department of Pharmacology, Toxicology and Therapeutics, KU Integrative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
Published online on: September 18, 2018 https://doi.org/10.3892/or.2018.6713
Pages: 3144-3154
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The poor treatment outcomes of pancreatic cancer are linked to an enrichment of cancer stem cells (CSCs) in these tumors, which are resistant to chemotherapy and promote metastasis and tumor recurrence. The present study investigated an extract from the root of the medicinal plant Rauwolfia vomitoria (Rau) for its activity against pancreatic CSCs. In vitro tumor spheroid formation and CSC markers were tested, and in vivo tumorigenicity was evaluated in nude mice. Rau inhibited the overall proliferation of human pancreatic cancer cell lines with a 50% inhibitory concentration (IC50) ranging between 125 and 325 µg/ml, and showed limited cytotoxicity towards normal epithelial cells. The pancreatic CSC population, identified using cell surface markers or a tumor spheroid formation assay, was significantly reduced, with an IC50 value of ~100 µg/ml treatment for 48 h and ~27 µg/ml for long-term tumor spheroid formation. The levels of CSC-related gene Nanog and nuclear β-catenin were decreased, suggesting suppression of the Wnt/β-catenin signaling pathway. In vivo, 20 mg/kg of Rau administered five times per week by oral gavage significantly reduced the tumorigenicity of PANC-1 cells in immunocompromised mice. Taken together, these data showed that Rau preferentially inhibited pancreatic cancer stem cells. Further investigation is warranted to examine the potential of Rau as a novel treatment for pancreatic cancer.

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