Espitia-Pérez Pedro Juan, Espitia-Perez Lyda Marcela, Negrette-Guzmán Mario
Facultad de Ciencias de la Salud, Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Montería 230001, Colombia.
Departamento de Ciencias Básicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga 680002, Colombia.
Int J Mol Sci. 2025 Jun 23;26(13):6013. doi: 10.3390/ijms26136013.
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.
由于肿瘤的异质性、可塑性和进展，前列腺癌（PCa）治疗面临挑战。代谢重编程作为一个动态过程，已成为PCa治疗的关键焦点。然而，针对癌症特异性代谢途径或使用化学增敏剂的传统疗法往往受到代偿机制和代谢复杂性的限制。本综述强调了转录因子，包括雄激素受体（AR）、p53、c-Myc、缺氧诱导因子-1（HIF-1）、核因子E2相关因子2（Nrf2）和过氧化物酶体增殖物激活受体γ（PPARγ），通过影响信号通路、酶和基因表达在调节PCa代谢中的作用。多靶点化合物，特别是天然产物，显示出破坏多种代谢酶的潜力，开辟了新的研究可能性。值得注意的例子包括β-榄香烯、胡桃醌、单宁酸和白藜芦醇A，它们通过酶抑制、转录因子调节、表观遗传变化和蛋白质相互作用破坏来靶向关键代谢过程。天然衍生的代谢产物可以在不同的代谢途径中引发横向反应，特别是在p53和MYC转录因子中。此外，五环萜类化合物（具有乌苏烷骨架的熊果酸）、萝卜硫素和异硫氰酸酯相关部分等化合物可能通过S-腺苷甲硫氨酸（SAM）和乙酰辅酶A调节诱导代谢和表观遗传变化，可能通过代谢过程影响新的研究领域。我们提出PCa中代谢重编程与转录因子/表观遗传调节之间存在协同串扰。这种方法具有扩展PCa治疗方法和开辟新研究途径的潜力。
