2. Academic Validation
  3. Discovery of Artemisinins as Microsomal Prostaglandins Synthase-2 Inhibitors for the Treatment of Colorectal Cancer via Chemoproteomics

Discovery of Artemisinins as Microsomal Prostaglandins Synthase-2 Inhibitors for the Treatment of Colorectal Cancer via Chemoproteomics

  • J Med Chem. 2024 Feb 8;67(3):2083-2094. doi: 10.1021/acs.jmedchem.3c01989.
Yiyun Geng 1 2,  Weichao Li 3,  Nai-Kei Wong 4,  Fuchong Xue 1,  Qing Li 1 2,  Yang Zhang 5,  Jingyuan Xu 1,  Zhangshuang Deng 2,  Yiqing Zhou 1 2
Affiliations

Affiliations

  • 1 School of Biotechnology and Food Engineering, Changshu Institute of Technology, Suzhou 215500, China.
  • 2 Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
  • 3 CAS Key Laboratory of Synthetic Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
  • 4 Clinical Pharmacology Section, Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.
  • 5 CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
PMID: 38287228 DOI: 10.1021/acs.jmedchem.3c01989
Abstract

Colorectal Cancer remains the second leading cause of cancer-related mortalities worldwide. While artemisinin (ART), a key active compound from the traditional Chinese medicinal herb Artemisia annua, has been recognized for its antiproliferative activity against colon Cancer cells, its underlying molecular underpinnings remain elusive. Whereas promiscuity of heme-dependent alkylating of macromolecules, mainly proteins, has been seen pivotal as a universal and primary mode of action of ART in Cancer cells, accumulating evidence suggests the existence of unique targets and mechanisms of actions contingent on cell or tissue specificities. Here, we employed photoaffinity probes to identify the specific targets responsible for ART's anti-colon Cancer actions. Upon validation, microsomal prostaglandins synthase-2 emerged as a specific and reversible target of ART in HCT116 colorectal Cancer cells, whose inhibition resulted in reduced cellular prostaglandin E2 biosynthesis and cell growth. Our discovery opens new opportunities for pharmacological treatment of colon Cancer.

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