Novel insights into the anti-cancer effects of 3-bromopyruvic acid against castration-resistant prostate cancer

Eur J Pharmacol. 2022 May 15:923:174929. doi: 10.1016/j.ejphar.2022.174929. Epub 2022 Mar 29.

Abstract

3-bromopyruvic acid (3-BP), a small molecule alkylating agent, has been emerged as a glycolytic inhibitor with anticancer activities. However, the effects of 3-BP on the growth and metastasis in prostate cancer have not been well investigated. Here we investigated the anti-cancer effects of 3-BP on prostate cancer in vitro and in vivo. Cell growth, apoptosis, migration, motility, and invasion were examined. The tumor growth ability was determined using a xenograft murine model. Transcriptome analysis using RNA-seq was performed to explore the mechanism of action of 3-BP. Our experimental results showed that 3-BP effectively inhibits prostate cancer cell growth, especially in castration-resistant prostate cancer (CRPC) cells. Moreover, 3-BP induces apoptosis and suppresses cell migration, motility, epithelial-mesenchymal transition (EMT), and invasion in CRPC cells. In addition, 3-BP also attenuates tumor growth in a xenograft murine model. Through transcriptome analysis using RNA-seq, 3-BP significantly regulates the cell cycle pathway and decreases the expression of downstream cycle cycle-associated genes in CRPC cells. The results of cell cycle analysis indicated that 3-BP arrests cell cycle progression at G2/M in CRPC cells. These results suggest that 3-BP has the potential in inhibiting CRPC progression and might be a promising drug for CRPC treatment.

Keywords: 3-Bromopyruvic acid; Anticancer; Cell metastasis; Prostate cancer; Transcriptome analysis.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Pyruvates
  • Xenograft Model Antitumor Assays

Substances

  • Pyruvates
  • bromopyruvate