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Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1.
Bioorg Chem 2019; 93:103315BC

Abstract

Glutamic-oxaloacetic transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements for sustained proliferation. As such, the GOT1 inhibitor may provide a new strategy for the treatment of various cancers. Adapalene has been approved by FDA for the treatment of acne, pimples and pustules, and it may also contribute to the adjunctive therapy for advanced stages of liver and colorectal cancers. In this work, we first examined the enzyme inhibition of over 500 compounds against GOT1 in vitro. As a result, Adapalene effectively inhibited GOT1 enzyme in a non-competitive manner. MST and DARTS assay further confirmed the high affinity between Adapalene and GOT1. Furthermore, the growth and migration of ovarian cancer ES-2 cells were obviously inhibited by the treatment of Adapalene. And it induced the apoptosis of ES-2 cells according to Western blot and Hoechst 33258 straining. In addition, molecular docking demonstrated that Adapalene coordinated in an allosteric site of GOT1 with low binding energy. Furthermore, knockdown of GOT1 in ES-2 cells decreased their anti-proliferative sensitivity to Adapalene. Together, our data strongly suggest Adapalene, as a GOT1 inhibitor, could be regarded as a potential drug candidate for ovarian cancer therapy.

Authors+Show Affiliations

Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: mengzhu_zheng@hust.edu.cn.Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: tjkeke@126.com.Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: syzyclx@163.com.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: li_hua@hust.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31605927

Citation

Wang, Qiqi, et al. "Adapalene Inhibits Ovarian Cancer ES-2 Cells Growth By Targeting Glutamic-oxaloacetic Transaminase 1." Bioorganic Chemistry, vol. 93, 2019, p. 103315.
Wang Q, Zhang Q, Luan S, et al. Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1. Bioorg Chem. 2019;93:103315.
Wang, Q., Zhang, Q., Luan, S., Yang, K., Zheng, M., Li, K., ... Li, H. (2019). Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1. Bioorganic Chemistry, 93, p. 103315. doi:10.1016/j.bioorg.2019.103315.
Wang Q, et al. Adapalene Inhibits Ovarian Cancer ES-2 Cells Growth By Targeting Glutamic-oxaloacetic Transaminase 1. Bioorg Chem. 2019;93:103315. PubMed PMID: 31605927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1. AU - Wang,Qiqi, AU - Zhang,Qingzhe, AU - Luan,Shanshan, AU - Yang,Kaiyin, AU - Zheng,Mengzhu, AU - Li,Kezhen, AU - Chen,Lixia, AU - Li,Hua, Y1 - 2019/09/26/ PY - 2019/04/21/received PY - 2019/08/13/revised PY - 2019/09/25/accepted PY - 2019/10/13/pubmed PY - 2019/10/13/medline PY - 2019/10/13/entrez KW - Adapalene KW - Drug repurposing KW - GOT1 inhibitor KW - Ovarian cancer SP - 103315 EP - 103315 JF - Bioorganic chemistry JO - Bioorg. Chem. VL - 93 N2 - Glutamic-oxaloacetic transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements for sustained proliferation. As such, the GOT1 inhibitor may provide a new strategy for the treatment of various cancers. Adapalene has been approved by FDA for the treatment of acne, pimples and pustules, and it may also contribute to the adjunctive therapy for advanced stages of liver and colorectal cancers. In this work, we first examined the enzyme inhibition of over 500 compounds against GOT1 in vitro. As a result, Adapalene effectively inhibited GOT1 enzyme in a non-competitive manner. MST and DARTS assay further confirmed the high affinity between Adapalene and GOT1. Furthermore, the growth and migration of ovarian cancer ES-2 cells were obviously inhibited by the treatment of Adapalene. And it induced the apoptosis of ES-2 cells according to Western blot and Hoechst 33258 straining. In addition, molecular docking demonstrated that Adapalene coordinated in an allosteric site of GOT1 with low binding energy. Furthermore, knockdown of GOT1 in ES-2 cells decreased their anti-proliferative sensitivity to Adapalene. Together, our data strongly suggest Adapalene, as a GOT1 inhibitor, could be regarded as a potential drug candidate for ovarian cancer therapy. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/31605927/Adapalene_inhibits_ovarian_cancer_ES-2_cells_growth_by_targeting_glutamic-oxaloacetic_transaminase_1 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(19)30615-7 DB - PRIME DP - Unbound Medicine ER -