Metastasis-associated protein 1-mediated antitumor and anticancer activity of dietary stilbenes for prostate cancer chemoprevention and therapy

Semin Cancer Biol. 2022 May:80:107-117. doi: 10.1016/j.semcancer.2020.02.012. Epub 2020 Feb 29.

Abstract

Dietary bioactive polyphenols that demonstrate beneficial biological functions including antioxidant, anti-inflammatory, and anticancer activity hold immense promise as effective and safe chemopreventive and chemosensitizing natural anticancer agents. The underlying molecular mechanisms of polyphenols' multiple effects are complex and these molecules are considered promising targets for chemoprevention and therapy. However, the development of novel personalized targeted chemopreventive and therapeutic strategies is essential for successful therapeutic outcomes. In this review, we highlight the potential of metastasis-associated protein 1 (MTA1)-targeted anticancer and antitumor effects of three dietary stilbenes, namely resveratrol, pterostilbene, and gnetin C, for prostate cancer management. MTA1, an epigenetic reader and master transcriptional regulator, plays a key role in all stages of prostate cancer progression and metastasis. Stilbenes inhibit MTA1 expression, disrupt the MTA1/histone deacetylase complex, modulate MTA1-associated Epi-miRNAs and reduce MTA1-dependent inflammation, cell survival, and metastasis in prostate cancer in vitro and in vivo. Overall, the MTA1-targeted strategies involving dietary stilbenes may be valuable for effective chemoprevention in selected subpopulations of early stage prostate cancer patients and for combinatorial strategies with conventional chemotherapeutic drugs against advanced metastatic prostate cancer.

Keywords: Chemoprevention; Dietary stilbenes; Gnetin C; MTA1; Natural products; Pharmacological targeting; Prostate cancer; Pterostilbene; Resveratrol; Therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Chemoprevention
  • Humans
  • Male
  • Polyphenols / therapeutic use
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / prevention & control
  • Repressor Proteins / metabolism
  • Stilbenes* / pharmacology
  • Stilbenes* / therapeutic use
  • Trans-Activators

Substances

  • MTA1 protein, human
  • Polyphenols
  • Repressor Proteins
  • Stilbenes
  • Trans-Activators