2. Academic Validation
  3. Withanolides from dietary tomatillo suppress HT1080 cancer cell growth by targeting mutant IDH1

Withanolides from dietary tomatillo suppress HT1080 cancer cell growth by targeting mutant IDH1

  • Bioorg Med Chem. 2021 Apr 15:36:116095. doi: 10.1016/j.bmc.2021.116095.
Yueying Yang 1,  Ke Xiang 1,  Dejuan Sun 1,  Mengzhu Zheng 2,  Zhuorui Song 1,  Mingxue Li 1,  Xuanbin Wang 3,  Hua Li 4,  Lixia Chen 5
Affiliations

Affiliations

  • 1 Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 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.
  • 3 Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan 442000, China. Electronic address: Wangxb@hbmu.edu.cn.
  • 4 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. Electronic address: li_hua@hust.edu.cn.
  • 5 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.
PMID: 33735687 DOI: 10.1016/j.bmc.2021.116095
Abstract

Isocitrate dehydrogenase (IDH) is one key rate-limiting Enzyme in the tricarboxylic acid cycle, which is related to various cancers. Tomatillo (Physalis ixocarpa), a special tomato, is widely consumed as nutritious vegetable in Mexico, USA, etc. As a rich source for withanolides, the fruits of P. ixocarpa were investigated, leading to the isolation of 11 type-A withanolides including 4 new ones (1 is an artificial withanolide). All these withanolides were evaluated for their inhibition on mutant IDH1 Enzyme activity. Among them, physalin F (11) exhibited potent Enzyme inhibitory activity and binding affinity with mutant IDH1. It inhibits the proliferation of HT1080 cells by selectively inhibiting the activity of mutant IDH1. Since Ixocarpalactone A, another major type-B withanolide in this plant, could act on another energy metabolism target PHGDH, the presence of different types of withanolides in tomatillo and their synergistic effect could make it a potential antitumor functional food or drug.

Keywords

Antitumor; HT1080; Mutant IDH1; Physalin F; Physalis ixocarpa; Type-A withanolide.

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