Cyp4z1: A Potential Target For Breast Cancer Treatment By Killing Cancer Stem Cells

• By: ZHENG, Lufeng (China Pharmaceutical University, China)
• Co-author(s): Dr Lufeng Zheng (China Pharmaceutical University, Nanjing, China)
  Dr Shengtao Xu
  
• Abstract:

  Objective: Breast cancer stem cells (BCSCs) are considered to be one of the roots contributing to the chemoresistance and metastasis in breast cancer. Our and other studies have shown that CYP4Z1 expression is increased in breast cancer tissues and positively correlated with breast cancer progression. This study aims to reveal the critical roles and underlying mechanisms of CYP4Z1 in the signal activation of BCSCs through CYP4Z1 transgenic mice and further screened out a better CYP4Z1 inhibitor. Methods: We constructed CYP4Z1 transgenic mice and combined with breast cancer spontaneous model MMTV-PyMT mice to reveal the effects of CYP4Z1 in breast cancer occurrence and progression. Additionally, the underlying mechanisms were elucidated using drug genomics, metabolomics, and molecular interaction analysis. Furthermore, we chemically synthesized and screened out CYP4Z1 inhibitors through enzyme activity detection. Results: CYP4Z1 was found to contribute to PyMT-induced breast cancer occurrence and progression. And compound 7c was screened out to be a better CYP4Z1 inhibitor, which can specifically kill BCSCs by targeting CYP4Z1. Conclusion: CYP4Z1 can be a novel drug target for breast cancer and compound 7c might be used for breast cancer treatment by targeting CYP4Z1. And compound 7c can be a novel lead compound for CYP4Z1 inhibitor.