Deciphering TGF-β1's role in drug resistance and leveraging plant bioactives for cancer therapy

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2025-02-05 DOI:10.1016/j.ejphar.2024.177218

Vishal Kumar Deb, Nidhi Chauhan, Utkarsh Jain

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引用次数: 0

Abstract

The intricate regulatory mechanisms governing TGF-β1 expression play pivotal roles in tumor progression. Key proteins such as FKBP1A, SMAD6, and SMAD7 trigger this process, modulating cell growth inhibition via p15INK4b and p21CIP1 induction. Despite TGF-β′s tumor-suppressive functions, cancer cells adeptly evade its effects, fueling disease advancement. Tumor microenvironmental TGF-β1 prompts epithelial-mesenchymal transition (EMT), facilitated by transcription factors like slug, twist-1, and snail. Notably, cancer-associated fibroblasts (CAFs) amplify this effect by secreting TGF-β1, fostering drug resistance. Of particular concern is the resistance observed with BRAF/MEK inhibitors (BRAFi/MEKi), highlighting the clinical significance of TGF-β signaling in cancer therapeutics. However, emerging interest in natural anti-cancer agents, with their distinct pharmacological actions on signaling proteins offers promising avenues for therapeutic intervention. This review emphasizes the multifaceted interplay between TGF-β signaling, tumor microenvironment dynamics, and therapeutic resistance mechanisms, illuminating potential targets for combating cancer progression by plant-derived-natural-bioactive compounds. However, this review additionally explores the currently available advanced methods for detecting various types of cancer. Not only that, but it also discussed the function of plant-derived compounds in clinical aspects, as well as its limitations.

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解读TGF-β1在耐药中的作用并利用植物生物活性物治疗癌症。

TGF-β1表达的复杂调控机制在肿瘤进展中起关键作用。FKBP1A、SMAD6和SMAD7等关键蛋白触发这一过程，通过p15INK4b和p21CIP1诱导调节细胞生长抑制。尽管TGF-β具有肿瘤抑制功能，但癌细胞熟练地逃避其作用，加速疾病进展。肿瘤微环境TGF-β1促进上皮-间质转化（EMT），由slug、twist-1和snail等转录因子促进。值得注意的是，癌症相关成纤维细胞（CAFs）通过分泌TGF-β1增强这种作用，促进耐药性。特别值得关注的是BRAF/MEK抑制剂（BRAFi/MEKi）的耐药性，这突出了TGF-β信号在癌症治疗中的临床意义。然而，人们对天然抗癌药物的兴趣日益浓厚，它们对信号蛋白具有独特的药理作用，为治疗干预提供了有希望的途径。本综述强调了TGF-β信号、肿瘤微环境动力学和治疗耐药机制之间的多方面相互作用，阐明了天然生物活性化合物对抗癌症进展的潜在靶点。然而，这篇综述还探讨了目前可用的检测各种类型癌症的先进方法。不仅如此，还讨论了植物源性化合物在临床方面的功能，以及其局限性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.