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

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

Author information

1
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
2
Department of Biotechnology, Korea National University of Transportation, 61 University Rd, Jeungpyeong, Chungbuk, 368-701, Korea.
3
Department of Applied Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
4
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.

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.

KEYWORDS:

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

PMID:
27605402
DOI:
10.1002/ptr.5708
[Indexed for MEDLINE]

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