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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to
Pedro Juan Espitia-Pérez1,2, Lyda Marcela Espitia-Perez1, Mario Negrette-Guzmán2
1Facultad de Ciencias de la Salud, Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Montería 230001, Colombia.
Abstract:
Prostate cancer (PCa) therapy faces challenges due to tumor heterogeneity, plasticity, and progression. Metabolic reprogramming, a dynamic process, has emerged as a key focus in PCa treatment. However, conventional therapies targeting cancer-specific metabolic pathways or employing chemosensitizers are often limited by compensatory mechanisms and metabolic complexity. This review highlights the roles of transcription factors, including AR, p53, c-Myc, HIF-1, Nrf2, and PPARγ, in regulating PCa metabolism by influencing signaling pathways, enzymes, and gene expression. Multi-target compounds, particularly natural products, show potential for disrupting multiple metabolic enzymes, opening up new research possibilities. Notable examples include β-elemene, juglone, tannic acid, and withaferin A, which target critical metabolic processes through enzyme inhibition, transcription factor modulation, epigenetic changes, and protein interaction disruption. Naturally derived metabolites can elicit transversal responses in diverse metabolic pathways, particularly in p53 and MYC transcription factors. Additionally, compounds such as pentacyclic terpenoids (ursolic acid with ursane skeleton), sulforaphane, and isothiocyanate-related moieties may induce metabolic and epigenetic changes through S-adenosyl methionine (SAM) and acetyl-CoA modulation, potentially affecting new areas of research through metabolic processes. We propose a cooperative crosstalk between metabolic reprogramming and transcription factors/epigenetic modulation in PCa. This approach holds potential for expanding PCa therapeutics and opening new avenues for research.
Insights
Metabolic reprogramming is key in prostate cancer (PCa) treatment. Natural compounds targeting transcription factors and metabolism offer new therapeutic avenues for PCa, overcoming treatment limitations.
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.
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