Natural products that target p53 for cancer therapy

J Nat Med. 2025 Jul;79(4):725-737. doi: 10.1007/s11418-025-01906-6. Epub 2025 Apr 28.

Abstract

Wild-type p53 acts as a tumor suppressor, but p53 is frequently mutated and inactivated in tumor cells, promoting cancer progression, invasion, and metastasis. Thus, compounds that reactivate p53 may be leveraged for cancer treatment, and the development of drugs targeting p53 reactivation is actively progressing. Notably, natural products exhibit diverse structures and biological activities and are used as therapeutic agents for various diseases worldwide. This review discusses the natural products that inhibit p53 degradation through p53-Mdm2 interaction, promote p53 reactivation by inducing conformational changes, and exhibit p53-dependent growth inhibition.

Keywords: Cancer therapy; Natural products; Tumor suppressor; p53 reactivation.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Biological Products* / chemistry
  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Tumor Suppressor Protein p53* / antagonists & inhibitors
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Biological Products
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-mdm2