2. Academic Validation
  3. A novel halogenated adenosine analog 5'-BrDA displays potent toxicity against colon cancer cells in vivo and in vitro

A novel halogenated adenosine analog 5'-BrDA displays potent toxicity against colon cancer cells in vivo and in vitro

  • Toxicol Appl Pharmacol. 2022 Feb 1:436:115857. doi: 10.1016/j.taap.2021.115857.
Long Ma 1,  Yingying Lu 2,  Yaqin Li 2,  Zhizhen Yang 2,  Yu Mao 3,  Yi Wang 4,  Shuli Man 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: [email protected].
  • 2 State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
  • 3 State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Collaborative Innovation Center of Advanced Microstructures, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
  • 4 State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Collaborative Innovation Center of Advanced Microstructures, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: [email protected].
PMID: 34979143 DOI: 10.1016/j.taap.2021.115857
Abstract

Adenosine, as a naturally occurring nucleoside, plays an important role in human health maintenance. In recent years, many studies have shown that adenosine has the effect of Cancer inhibition, and some of its analogs have been successfully marketed as Anticancer drugs. This report mainly describes the anti-colon Cancer activities and mechanism of a novel halogenated adenosine analog named 5'-bromodeoxyadenosine (5'-BrDA). As a result, 5'-BrDA concentration-dependently inhibited colon Cancer cells proliferation, induced Autophagy without disruption of lysosomal stability, and promoted autophagy-independently cellular mitochondrial Apoptosis by increasing the accumulation of Reactive Oxygen Species. Furthermore, 5'-BrDA inhibited the tumor growth of colon Cancer in CT26 inbred mice without affecting the body weight in vivo. Collectively, the above-mentioned mechanisms contributed to the Anticancer activity of 5'-BrDA. It is rare to discover novel Anticancer adenosine analogs during the past couple of decades. We believe that our work will enrich the understanding of adenosine analogs, also, pave the way for adenosine analogs product based Anticancer drug development.

Keywords

Anti-colon cancer; Apoptosis; Autophagy; Halogenated adenosine analogue; ROS overproduction.

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