Angelica gigas Nakai Has Synergetic Effects on Doxorubicin-Induced Apoptosis.

Yong-Joon Jeon,Jong-Il Shin,Ye Sun Han,Hak Cheol Kwon,Yoon Gyeong Lee,Ji Beom Kim,Kyungho Lee,Inki Kim,Sol Lee,Sung Hun Kim

doi:10.1155/2018/6716547

Abstract

Natural products are valuable sources for drug discovery because they have a wide variety of useful chemical components and biological properties. A quick reevaluation of the potential therapeutic properties of established natural products was made possible by the recent development of the methodology and improvement in the accuracy of an automated high-throughput screening system. In this study, we screened natural product libraries to detect compounds with anticancer effects using HeLa cells. Of the 420 plant extracts screened, the extract of Angelica gigas Nakai (AGN) was the most effective in reducing cell viability of HeLa cells. Markers of apoptosis, such as exposure of phosphatidylserine and cleavage of caspase-7 and PARP, were increased by treatment with the AGN extract. Treatment of the AGN extract increased expression of PKR as well as ATF4 and CHOP, the unfolded protein response genes. In addition, cotreatment of doxorubicin and the AGN extract significantly increased doxorubicin-induced apoptosis in HeLa cells. Decursin and decursinol angelate, which were known to have anticancer effects, were the main components of the AGN extract. These results suggest that the extract of AGN containing, decursin and decursinol angelate, increases doxorubicin susceptibility.

Highlights

Doxorubicin, belonging to the anthracycline group, was initially derived from Streptomyces peucetius in the 1960s [1]
As the cell death induced by doxorubicin was related to eIF2α phosphorylation, we investigated the synergetic effect between doxorubicin and the Angelica gigas Nakai (AGN) extract
Since recent studies have shown that cancer and inflammation are closely related [26], in this study we investigated the anticancer effects of natural product extracts from the KIST Natural Product Library

Summary

Introduction

Doxorubicin (adriamycin), belonging to the anthracycline group, was initially derived from Streptomyces peucetius in the 1960s [1]. Owing to its wide range of anticancer effects against various types of cancers, including solid tumors and hematological malignancies, doxorubicin has occupied an important place in chemotherapy [2, 3]. The application of doxorubicin, has many side effects including cardiac toxicity; the dose of doxorubicin has been limited [4]. Multidrug resistance or chemoresistance prompted by chemotherapy reduced doxorubicin susceptibility, further limiting its use [5]. Despite these disadvantages, doxorubicin is still an attractive chemotherapeutic drug. To use doxorubicin more efficiently, various therapies have been proposed, including the use of combination therapy as a treatment strategy. Chemotherapy regimens using doxorubicin, such as FAC (fluorouracil, doxorubicin, and cyclophosphamide), TAC (docetaxel, doxorubicin, and cyclophosphamide), and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), have been administered to cancer patients [6, 7]

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Conclusion