Extract of the Medicinal Plant Pao Pereira Inhibits Pancreatic Cancer Stem-Like Cell In Vitro and In Vivo

Integr Cancer Ther. 2018 Dec;17(4):1204-1215. doi: 10.1177/1534735418786027. Epub 2018 Jul 9.

Abstract

Pancreatic cancers are enriched with cancer stem-like cells (CSCs), which are resistant to chemotherapies, and responsible for tumor metastasis and recurrence. Here, we investigated the extract of a medicinal plant Pao Pereira (Pao) for its activity against pancreatic CSCs. Pao inhibited overall proliferation of human pancreatic cancer cell lines with IC50 ranging from 125 to 325 μg/mL and had limited cytotoxicity to normal epithelial cells. Pancreatic CSC population, identified using surface markers CD24+ CD44+ EpCam+ or tumor spheroid formation assay, was significantly reduced, with IC50s of ~100 μg/mL for 48 hours treatment, and ~27 μg/mL for long-term treatment. Nuclear β-catenin levels were decreased, suggesting suppression of Wnt/β-catenin signaling pathway. In vivo, Pao at 20 mg/kg, 5 times/week gavage, significantly reduced tumorigenicity of PANC-1 cells in immunocompromised mice, indicating inhibition of CSCs in vivo. Further investigation is warranted in using Pao as a novel treatment targeting pancreatic CSCs.

Keywords: Pao Pereira; cancer stem-like cells; pancreatic cancer; xenograft models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD24 Antigen / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Epithelial Cell Adhesion Molecule / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Mice
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry*
  • Signal Transduction / drug effects
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / metabolism

Substances

  • CD24 Antigen
  • Epithelial Cell Adhesion Molecule
  • Hyaluronan Receptors
  • Plant Extracts
  • beta Catenin