Decursin in Angelica gigas Nakai (AGN) Enhances Doxorubicin Chemosensitivity in NCI/ADR-RES Ovarian Cancer Cells via Inhibition of P-glycoprotein Expression

Phytother Res. 2016 Dec;30(12):2020-2026. doi: 10.1002/ptr.5708. Epub 2016 Sep 8.

Abstract

Angelica gigas Nakai (AGN, Korean Dang-gui) is traditionally used for the treatment of various diseases including cancer. Here, we investigated multidrug-resistant phenotype-reversal activities of AGN and its compounds (decursin, ferulic acid, and nodakenin) in doxorubicin-resistant NCI/ADR-RES ovarian cancer cells. Our results showed that a combination of doxorubicin with either AGN or decursin inhibited a proliferation of NCI/ADR-RES cells. These combinations increased the number of cells at sub-G1 phase when cells were stained with Annexin V-fluorescein isothiocyanate. We also found that these combinations activated caspase-9, caspase-8, and caspase-3 and increased cleaved PARP level. Moreover, an inhibition of P-glycoprotein expression by either AGN or decursin resulted in a reduction of its activity in NCI/ADR-RES cells. Therefore, our data demonstrate that decursin in AGN inhibits doxorubicin-resistant ovarian cancer cell proliferation and induces apoptosis in the presence of doxorubicin via blocking P-glycoprotein expression. Therefore, AGN would be a potentially novel treatment option for multidrug-resistant tumors by sensitizing to anticancer agents. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: Angelica gigas Nakai; P-glycoprotein; apoptosis; decursin; doxorubicin-resistant ovarian cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism*
  • Angelica / chemistry*
  • Apoptosis
  • Benzopyrans / chemistry*
  • Butyrates / chemistry*
  • Cell Proliferation
  • Doxorubicin / pharmacology*
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Benzopyrans
  • Butyrates
  • Doxorubicin
  • decursin