Furanodiene presents synergistic anti-proliferative activity with paclitaxel via altering cell cycle and integrin signaling in 95-D lung cancer cells

Phytother Res. 2014 Feb;28(2):296-9. doi: 10.1002/ptr.4984. Epub 2013 Apr 3.

Abstract

Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Recently, we found that the combined treatment of FUR with paclitaxel (TAX) showed synergetic anti-proliferative activities in 95-D lung cancer cells. Herein, we showed that FUR reduced the cell numbers distributed in mitosis phase induced by TAX while increased those in G1 phase. The protein levels of cyclin D1, cyclin B1, CDK6 and c-Myc were all down-regulated in the group of combined treatment. The dramatically down-regulated expression of integrin β4, focal adhesion kinase and paxillin might partially contribute to the synergic effect. Though FUR alone obviously induced endoplasmic reticulum stress, this signaling pathway may not contribute to the synergetic anti-proliferative effect as the protein expression of CHOP and BIP was similar in FUR alone and combined treatment group.

Keywords: cell cycle; furanodiene; integrin β4; lung cancer; paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Curcuma / chemistry
  • Cyclin B1 / metabolism
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 6 / metabolism
  • Drug Synergism
  • Drugs, Chinese Herbal / pharmacology
  • Endoplasmic Reticulum Stress
  • Focal Adhesion Kinase 1 / metabolism
  • Furans / pharmacology*
  • Heterocyclic Compounds, 2-Ring / pharmacology*
  • Humans
  • Integrin beta4 / metabolism*
  • Lung Neoplasms / metabolism*
  • Paclitaxel / pharmacology*
  • Paxillin / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction / drug effects*

Substances

  • CCNB1 protein, human
  • CCND1 protein, human
  • Cyclin B1
  • Drugs, Chinese Herbal
  • Furans
  • Heterocyclic Compounds, 2-Ring
  • Integrin beta4
  • MYC protein, human
  • PXN protein, human
  • Paxillin
  • Proto-Oncogene Proteins c-myc
  • Cyclin D1
  • furanodiene
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6
  • Paclitaxel