1-Benzylimidazole attenuates the stemness of breast cancer cells through partially targeting CYP4Z1

  • Environ Toxicol. 2023 Nov 23. doi: 10.1002/tox.24050.
Hai Qin  1 Yi Zhou  2 Hai Liu  2 Yaqin Yuan  3 Qianqian Guo  4 Manqin Yuan  5 Tao Xi  2 Yujie Zhang  1
Affiliations
  • 1. Department of Clinical Laboratory, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang City, Guizhou, China.
  • 2. School of Life Science and Technology, School of Engineering, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.
  • 3. Microbiological Laboratory, Guizhou Center For Medical Device Testing, Guiyang, Guizhou, China.
  • 4. Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People's Republic of China.
  • 5. Department of Clinical Laboratory Medicine, Guizhou Medical University, Guiyang, Guizhou, China.
Abstract

Cytochrome P450 (CYP) 4Z1 (CYP4Z1) has recently garnered much interest as its expression predicts a poor prognosis and as a oncogene in breast Cancer, and overexpressed in Other many cancers. We previously showed that CYP4Z1 acts as a promoter of Cancer Stem Cells (CSCs) to facilitate the occurrence and development of breast Cancer. Here, RNA Sequencing found that 1-benzylimidazole (1-Benzy) held a preferable correlation with breast Cancer and suppressed the expression of CSC makers. Further functional experiments, including mammary spheroid formation, wound-healing, transwell-invasion, detection of tumor initiation, and metastatic ability, showed that 1-Benzy suppressed the stemness and metastasis of breast Cancer cells. Additionally, we further demonstrated that CYP4Z1 is necessary for 1-Benzy-mediated suppression on breast Cancer stemness and 1-Benzy exerted a weaker effect in breast Cancer cells with CYP4Z1 knockdown. Taken together, our data suggest that 1-Benzy might be a potential drug suppressing breast Cancer stemness via targeting CYP4Z1.

Keywords
1-benzylimidazole; CYP4Z1; breast cancer; cancer stem cell; small-molecule inhibitor.
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