Natural anthraquinone compound emodin as a novel inhibitor of aurora A kinase: A pilot study

Fen-Lan Wu; Pei-Yi Chu; Guan-Yu Chen; Ke Wang; Wei-Yu Hsu; Azaj Ahmed; Wen-Lung Ma; Wei-Chung Cheng; Yang-Chang Wu; Juan-Cheng Yang

doi:10.1111/cbdd.13938

Back

Natural anthraquinone compound emodin as a novel inhibitor of aurora A kinase: A pilot study

Journal article

Peer reviewed

Natural anthraquinone compound emodin as a novel inhibitor of aurora A kinase: A pilot study

Fen-Lan Wu, Pei-Yi Chu, Guan-Yu Chen, Ke Wang, Wei-Yu Hsu, Azaj Ahmed, Wen-Lung Ma, Wei-Chung Cheng, Yang-Chang Wu and Juan-Cheng Yang

Chemical biology & drug design, Vol.99(1), pp.126-135

01/2022

DOI: 10.1111/cbdd.13938

PMID: 34411446

View Online

Abstract

Aurora kinase A (AURKA) carries out an essential role in proliferation and involves in cisplatin resistance in various cancer cells. Overexpression of AURKA is associated with the poor prognosis of cancer patients. Thus, AURKA has been considered as a target for cancer therapy. Developing AURKA inhibitors became an important issue in cancer therapy. A natural compound emodin mainly extracted from rhubarbs possesses anti-cancer properties. However, the effect of emodin on AURKA has never been investigated. In the present study, molecular docking analysis indicated that emodin interacts with AURKA protein active site. We also found nine emodin analogues from Key Organic database by using ChemBioFinder software. Among that, one analogue 8L-902 showed a similar anti-cancer effect as emodin. The bindings of emodin and 8L-902 on AURKA protein were confirmed by cellular thermal shift assay. Furthermore, emodin inhibited the AURKA kinase activity in vitro and enhanced the cisplatin-DNA adduct level in a resistant ovarian cancer cell line. It seems that emodin may have the potential to inhibit cancer cell growth and enhance cisplatin therapy in cancer with resistance. Collectively, our finding reveals a novel AURKA inhibitor, emodin, which may be vulnerable to ovarian cancer therapy in the future.

Anthraquinones - chemistry

Anthraquinones - metabolism

Anthraquinones - pharmacology

Aurora Kinase A - antagonists & inhibitors

Aurora Kinase A - metabolism

Binding Sites

Catalytic Domain

Cell Line, Tumor

Cell Survival - drug effects

Cisplatin - analysis

Cisplatin - chemistry

Cisplatin - pharmacology

Databases, Chemical

DNA Adducts - analysis

Emodin - analogs & derivatives

Emodin - metabolism

Emodin - pharmacology

Gene Expression Regulation, Neoplastic - drug effects

Humans

Molecular Docking Simulation

Pilot Projects

Protein Binding

Protein Kinase Inhibitors - chemistry

Protein Kinase Inhibitors - metabolism

Protein Kinase Inhibitors - pharmacology

Temperature

Details

Title: Subtitle: Natural anthraquinone compound emodin as a novel inhibitor of aurora A kinase: A pilot study
Creators: Fen-Lan Wu - Nanjing Medical University
Pei-Yi Chu - Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
Guan-Yu Chen - Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
Ke Wang - China Medical University
Wei-Yu Hsu - Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
Azaj Ahmed - China Medical University
Wen-Lung Ma - Sex Hormone Research Center, Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan
Wei-Chung Cheng - Graduate Institute of Biomedical Sciences, Graduate Institution of Cancer Biology, Graduate Institute of Public Health, China Medical University, Taichung, Taiwan
Yang-Chang Wu - Graduate Institute of Integrated Medicine, School of Chinese Medicine, China Medical University, Taichung, Taiwan
Juan-Cheng Yang - Graduate Institute of Integrated Medicine, School of Chinese Medicine, China Medical University, Taichung, Taiwan
Resource Type: Journal article
Publication Details: Chemical biology & drug design, Vol.99(1), pp.126-135
DOI: 10.1111/cbdd.13938
PMID: 34411446
ISSN: 1747-0277
eISSN: 1747-0285
Grant note: Ministry of Science and Technology China Medical University, Taiwan
Language: English
Date published: 01/2022
Academic Unit: Internal Medicine
Record Identifier: 9985178666602771

Metrics

1 Record Views

7 Times Cited - Web of Science

See more details