Tanshinone analog inhibits castration-resistant prostate cancer cell growth by inhibiting glycolysis in an AR-dependent manner

• DOI: 10.1016/j.jbc.2024.107139
• Publication Date: 2024-03-05T02:23:12Z
• Authors: Jia Yu; Shengyou Li; Sha Cheng; Mashaal Ahmad; Chao Chen; Xinwei Wan; Shinan Wei; Weidong Pan; Heng Luo

Androgen receptor (AR) is one of the key targets for treatment Castration-resistant prostate cancer (CRPC). Current endocrine therapy can greatly improve CRPC patients. However, with change pathogenic mechanism, acquired resistance often leads to failure treatment. Studies have shown that tanshinone IIA (TS-IIA) and its derivatives significant antitumor activity, certain AR targeting effects, but mechanism unknown. In this study, TS-IIA analog TB3 was found significantly inhibit growth in vitro vivo. Molecular docking, cellular thermal shift assay CHX experiments confirmed target promoted degradation AR. Furthermore, glycolysis metabolism by AR/PKM2 axis..The addition pyruvic acid could alleviate inhibitory effect on cells. Besides, knockdown or PKM2 also reverse Taken together, our study suggests derivative inhibits prevent process axis.