PT  - JOURNAL ARTICLE
AU  - LIJUAN BAI
AU  - XIN LI
AU  - XIAOWEI MA
AU  - RUI ZHAO
AU  - DAQING WU
TI  - <em>In Vitro</em> Effect and Mechanism of Action of Ergot Alkaloid Dihydroergocristine in Chemoresistant Prostate Cancer Cells
AID  - 10.21873/anticanres.14626
DP  - 2020 Nov 01
TA  - Anticancer Research
PG  - 6051--6062
VI  - 40
IP  - 11
4099  - http://ar.iiarjournals.org/content/40/11/6051.short
4100  - http://ar.iiarjournals.org/content/40/11/6051.full
SO  - Anticancer Res2020 Nov 01; 40
AB  - Background/Aim: Chemoresistance is a major obstacle in the treatment of prostate cancer (PCa). It is imperative to develop novel strategies for overcoming chemoresistance and improving clinical outcomes. We evaluated the in vitro activity and mechanism of action of dihydroergocristine (DHECS), an ergot alkaloid approved for the treatment of dementia, in PCa cells. Materials and Methods: The in vitro effects of DHECS on PCa cell cycle and viability were determined by flow cytometry and colorimetric assay. The effects of DHECS on PCa cell signaling were evaluated by quantitative PCR, western blot analysis and reporter assay. Results: DHECS was effective in inducing cell cycle arrest and apoptosis in human PCa cells. Of particular interest, DHECS demonstrated high potency against chemoresistant PCa cells. At the molecular level, DHECS affected multiple factors implicated in the regulation of cancer cell cycle and programmed cell death, including p53, mouse double minute 2 homolog (MDM2), retinoblastoma protein (RB), p21, E2F transcription factor 1 (E2F1), survivin, myeloid cell leukemia 1 (Mcl-1) and poly ADP ribose polymerase (PARP). Furthermore, DHECS may function through dopamine receptor-mediated effects on 5’-AMP-activated protein kinase (AMPK) and nuclear factor kappa B (NF-ĸB). Conclusion: DHECS has the potential to be repurposed as a novel anticancer agent for the management of chemoresistant PCa.