Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to...

Area of Science:

• Oncology
• Metabolic pathways
• Cancer biology

Background:

• Prostate cancer (PCa) exhibits tumor heterogeneity and plasticity, complicating treatment.
• Metabolic reprogramming is a critical hallmark of PCa, influencing disease progression.
• Conventional therapies face limitations due to compensatory metabolic mechanisms in cancer cells.

Purpose of the Study:

• To review the role of transcription factors in regulating PCa metabolism.
• To explore the potential of multi-target compounds, especially natural products, in PCa therapy.
• To highlight the interplay between metabolic reprogramming and transcription factor/epigenetic modulation in PCa.

Main Methods:

• Literature review focusing on transcription factors (AR, p53, c-Myc, HIF-1, Nrf2, PPARγ) and their metabolic roles in PCa.
• Analysis of natural products (e.g., β-elemene, juglone, tannic acid, withaferin A) targeting metabolic pathways and transcription factors.
• Investigation of compounds modulating S-adenosyl methionine (SAM) and acetyl-CoA for epigenetic effects.

Main Results:

• Transcription factors significantly regulate PCa metabolism by influencing signaling pathways and gene expression.
• Natural products demonstrate potential by inhibiting metabolic enzymes, modulating transcription factors, and inducing epigenetic changes.
• Compounds like β-elemene, juglone, tannic acid, and withaferin A show promise in disrupting critical metabolic processes.
• Naturally derived metabolites can impact p53 and MYC transcription factors, offering broad metabolic pathway effects.
• Certain compounds induce metabolic and epigenetic changes via SAM and acetyl-CoA modulation.

Conclusions:

• A cooperative crosstalk exists between metabolic reprogramming and transcription factor/epigenetic modulation in PCa.
• Targeting this interplay presents a promising strategy for expanding PCa therapeutics.
• Natural products offer a valuable resource for developing novel multi-target agents against PCa.