Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics

Molecules. 2015 Oct 2;20(10):18066-82. doi: 10.3390/molecules201018066.

Abstract

Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity.

Keywords: Chamaecyparis obtusa; anthricin; gas chromatography-mass spectrometry; human colorectal cancer; metabolite profiling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chamaecyparis / chemistry*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Gas Chromatography-Mass Spectrometry / methods*
  • HCT116 Cells
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Metabolomics / methods*
  • Methanol / chemistry
  • Methanol / pharmacology
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Plant Leaves / chemistry
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Heterocyclic Compounds, 4 or More Rings
  • Plant Extracts
  • anthricin
  • JNK Mitogen-Activated Protein Kinases
  • Methanol