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

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.

Decursin inhibits the growth of HepG2 hepatocellular carcinoma cells via Hippo/YAP signaling pathway

“…Recently, drugs derived from the medicinal herb are popular around the world and have become a hot area of research. Decursin, a major compound isolated from the root of the Korean Dang‐gui ( Angelica gigas Nakai, AGN), was used to treat various diseases, which shows activities of antiliver fibrosis (Y. J. Choi et al, ), anticancer (J. H. Kim, Jung, Kim, & Jeong, ; J. M. Kim et al, ; W. J. Kim, Lee, Choi, & Moon, ), and anticancer therapy sensitization (H. S. Choi et al, ; J. Kim et al, ). Most importantly, previous study also indicated that decursin shows low cytotoxicity to normal tissue as a cancer‐targeted therapy agent (Lee et al, ).…”

Peiminine serves as an adriamycin chemosensitizer in gastric cancer by modulating the EGFR/FAK pathway

“…For example, gambogenic acid has been reported to increase the chemosensitivity of breast cancer cells to ADR via suppressing the PTEN/PI3K/AKT pathway (10). Meanwhile, Choi et al revealed that decursin found in Angelica gigas Nakai (AGN) could inhibit the proliferation of ADR-resistant ovarian cancer cells and induce apoptosis in the presence of ADR via blocking P-glycoprotein expression (11).…”

Development of Resveratrol-Loaded Herbal Extract-Based Nanocomposites and Their Application to the Therapy of Ovarian Cancer

“…The antiproliferation potentials of AGN/RSV NPs were evaluated in SKOV-3 cells by a colorimetric assay ( Figure 6 and Table 2 ). The anticancer activities of ingredients and extracts of AGN against ovarian cancer cells were already reported somewhere [ 20 ]. In our previous report [ 24 ], the antiproliferation efficiency of AGN nanoformulation in breast cancer cells (that is, MCF-7 cells) was demonstrated.…”

“…Among diverse phytomedicines for cancer prevention and therapy [ 16 , 17 , 18 ], the pharmacological effects of single components and extracts of Angelica gigas Nakai (AGN) have been widely investigated [ 19 ]. The main components of AGN, such as decursin (D) and decursinol angelate (DA), and its extracts have anticancer potentials in several types of cancers, such as breast, blood, cervical, colon, lung, oral, ovarian, prostate, and skin cancers [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. In our previous studies [ 22 , 24 , 26 ], AGN extract and AGN particles have shown anticancer activities in breast, buccal, and cervical cancers.…”