Deciphering the mechanism of baicalein in cervical cancer via bioinformatics, machine learning and computational simulations: PIM1 and CDK2 are key target proteins.

Journal: International journal of biological macromolecules
Published Date:

Abstract

Cervical cancer is one of the leading causes of death among women worldwide. Current treatments are limited by chemoresistance and chemotherapeutic agents' adverse effects, prompting the search for better therapeutic alternatives. Baicalein, a natural compound with potent antitumor activity and low toxicity, has drawn significant attention. However, the precise mechanisms of baicalein against cervical cancer remain to be fully elucidated. In this study, bioinformatics and machine learning algorithms predicted six potential core targets of baicalein against cervical cancer. Molecular docking and molecular dynamics simulations were employed to further validate these targets, with a focus on assessing their binding affinity and stability. The molecular docking results demonstrated that five of the core targets exhibited significant binding affinity with baicalein. Notably, PIM1 and CDK2 showed stable binding conformations in molecular dynamics simulations. GO and KEGG enrichment analyses indicated baicalein might regulate cell cycle progression via histone kinase - mediated phosphorylation modifications. Thus, baicalein likely suppresses cervical cancer cells' abnormal proliferation by inhibiting PIM1 and CDK2 activity, inducing cell cycle arrest.

Authors

  • Shuyue Wang
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Cen Liu
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Danyang Ye
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Jinchai Qi
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Yantao Xing
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Jiahui Wang
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Xiaoxiao Fan
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Xiaojing Li
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Heng Chen
    Medical College, Guizhou University, Jiaxiu Road, Huaxi Zone, Guiyang 550025, P. R. China.
  • Hao Liu
    Key Laboratory of Development and Maternal and Child Diseases of Sichuan Province, Department of Pediatrics, Sichuan University, Chengdu, China.
  • Shuqi Li
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Shaojun Yu
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
  • Yonggang Liu
    School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China. Electronic address: liuyg0228@163.com.