Bromocriptine monotherapy overcomes prostate cancer chemoresistance in preclinical models

• DOI: 10.1016/j.tranon.2023.101707
• Publication Date: 2023-06-02T18:34:35Z
• Authors: Lijuan Bai; Xin Li; Yang Yang; Rui Zhao; Elshaddai Z. White; Alira Danaher; Nathan J. Bowen; Cimona V. Hinton; Nicholas Cook; Dehong Li; Alyssa Y. Wu; Min Qui; Yuhong Du; Haian Fu; Omer Kucuk; Daqing Wu
• Keywords: Survivin; Palbociclib

Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It imperative to develop novel strategies overcome chemoresistance and improve outcomes patients who have failed chemotherapy. Using two-tier phenotypic screening platform, we identified bromocriptine mesylate as potent selective inhibitor chemoresistant PCa cells. Bromocriptine effectively induced cell cycle arrest activated apoptosis cells but not chemoresponsive RNA-seq analyses revealed that affected subset genes implicated regulation cycle, DNA repair, death. Interestingly, approximately one-third (50/157) differentially expressed by overlapped with known p53-p21- retinoblastoma protein (RB) target genes. At level, increased expression dopamine D2 receptor (DRD2) several classical non-classical signal pathways cells, including adenosine monophosphate-activated kinase (AMPK), p38 mitogen-activated (p38 MAPK), nuclear factor kappa B (NF-κB), enhancer zeste homolog 2 (EZH2), survivin. As monotherapy, treatment at 15 mg/kg, three times per week, via intraperitoneal route significantly inhibited skeletal growth C4-2B-TaxR xenografts athymic nude mice. In summary, these results provided first preclinical evidence effective PCa. Due its favorable safety profiles, could be rapidly tested repurposed subtype-specific chemoresistance.