Paris Polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin

Molecules. 2019 Jun 3;24(11):2102. doi: 10.3390/molecules24112102.

Abstract

Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.

Keywords: DLD-1 cells; chemotherapy; doxorubicin; drug resistance; folk medicine.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Autophagy* / drug effects
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Ethanol / chemistry
  • Humans
  • Plant Extracts / therapeutic use

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Drugs, Chinese Herbal
  • Plant Extracts
  • Ethanol
  • Doxorubicin