Miconazole as a Repurposed Anticancer Candidate for Prostate Cancer

Area of Science:

• Oncology
• Pharmacology
• Drug Repurposing

Background:

• Prostate cancer presents significant global health challenges, marked by rising incidence and treatment resistance.
• Current therapies for prostate cancer often result in long-term side effects, necessitating innovative and safer treatment options.

Purpose of the Study:

• To investigate the potential of repurposing FDA-approved antifungal agents as novel prostate cancer therapeutics.
• To identify which of the tested antifungal agents exhibits the most significant anti-prostate cancer activity.

Main Methods:

• Five FDA-approved antifungal agents (natamycin, terbinafine hydrochloride, ketoconazole, miconazole, clotrimazole) were screened for their effects on prostate cancer cells.
• Miconazole (MZ) was further analyzed using proteomic profiling, microscopy, flow cytometry, and protein expression analysis to elucidate its mechanism of action.

Main Results:

• Miconazole (MZ) demonstrated superior efficacy in reducing prostate cancer cell viability, clonogenic growth, invasion, and migration compared to other agents.
• Proteomic analysis revealed that MZ modulates cell-cycle progression and apoptotic pathways, including p53 signaling.
• MZ treatment led to G0/G1 cell-cycle arrest by downregulating key proteins (cyclin D3, CDK2, CDK4, PCNA) and activating p53-associated signaling (increased p21, p27).

Conclusions:

• Miconazole (MZ) is identified as a mechanistically active repurposed drug candidate for prostate cancer.
• These findings support further research into drug repurposing strategies for oncology, specifically utilizing antifungal agents.