Ainsliadimer A induces ROS-mediated apoptosis in colorectal cancer cells via directly targeting peroxiredoxin 1 and 2.

The peroxiredoxin (PRDX) family is a class of antioxidant enzymes with peroxidase activity. Human PRDXs currently have six members (PRDX1-6), which are gradually becoming potential therapeutic targets for major diseases such as cancer. In this study, we reported ainsliadimer A (AIN), a sesquiterpene lactone dimer with antitumor activity. We found that AIN directly targets Cys173 of PRDX1 and Cys172 of PRDX2 and then inhibits their peroxidase activities. As a result, the level of intracellular ROS increases, causing oxidative stress damage in mitochondria, inhibiting mitochondrial respiration, and significantly inhibiting ATP production. AIN inhibits the proliferation and induces apoptosis of colorectal cancer cells. Additionally, it inhibits tumor growth in mice and the growth of tumor organoid models. Therefore, AIN can be one of the natural compounds targeting PRDX1 and PRDX2 in the treatment of colorectal cancer. Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Citation

Chao Lv, Yun Huang, Qun Wang, Chengji Wang, Hongmei Hu, Hongwei Zhang, Dong Lu, Honghong Jiang, Ruling Shen, Weidong Zhang, Sanhong Liu. Ainsliadimer A induces ROS-mediated apoptosis in colorectal cancer cells via directly targeting peroxiredoxin 1 and 2. Cell chemical biology. 2023 Mar 16;30(3):295-307.e5

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PMID: 36889312

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