Decursin in Angelica gigas Nakai (AGN) Enhances Doxorubicin Chemosensitivity in NCI/ADR-RES Ovarian Cancer Cells via Inhibition of P-glycoprotein Expression.
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.
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Hyeong Sim
HS
Choi
Department of Biotechnology, Korea National University of Transportation, 61 University Rd, Jeungpyeong, Chungbuk, 368-701, Korea.
Sung-Gook
SG
Cho
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Min Kyoung
MK
Kim
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Min Soo
MS
Kim
Department of Applied Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Seung Hee
SH
Moon
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Il Hwan
IH
Kim
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Seong-Gyu
SG
Ko
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D029969:Angelica / Q000737:chemistry*; D017209:Apoptosis; D001578:Benzopyrans / Q000737:chemistry*; D002087:Butyrates / Q000737:chemistry*; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*
D018435:ATP Binding Cassette Transporter, Subfamily B; D001578:Benzopyrans; D002087:Butyrates; D004317:Doxorubicin; C101278:decursin
Angelica gigas Nakai; P-glycoprotein; apoptosis; decursin; doxorubicin-resistant ovarian cancer