Identification of evodiamine as a suppressor of prostate cancer progression by reducing AR transcriptional activity...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Evodiamine (EVO) is a natural alkaloid with demonstrated antitumor properties against various cancers, including prostate cancer (PCa).
• The precise molecular mechanisms of evodiamine's anti-PCa effects, particularly its interaction with key signaling pathways, require further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the anti-prostate cancer (PCa) effects of evodiamine (EVO).
• To determine if evodiamine targets steroid receptor coactivator (Src) and its impact on androgen receptor (AR) signaling in PCa cells.

Main Methods:

• In vitro assays (MTT, colony formation, transwell) assessed cell proliferation, colony formation, migration, and invasion.
• In vivo animal studies evaluated evodiamine's effect on tumor growth.
• Western blot, qRT-PCR, ELISA, Co-Immunoprecipitation (CoIP), and dual-luciferase reporter assays were used to detect protein expression, gene expression, and AR transcriptional activity.

Main Results:

• Evodiamine significantly reduced proliferation, colony formation, migration, and invasion of PCa cells (LNCaP and 22Rv1) induced by dihydrotestosterone (DHT), and diminished tumor growth in vivo.
• Evodiamine directly targeted and reduced DHT-induced activation of steroid receptor coactivator (Src).
• Restoration of Src activation abrogated evodiamine's inhibitory effects, and evodiamine inhibited DHT-induced AR transcriptional activity by targeting Src.

Conclusions:

• Evodiamine exhibits significant antitumor activity against prostate cancer (PCa) by blocking androgen receptor (AR) transcriptional activity.
• The mechanism involves evodiamine targeting steroid receptor coactivator (Src), thereby inhibiting AR signaling.
• These findings support the development of evodiamine as a potential therapeutic agent for PCa.