Al Amin Md, Bouhenni Hasna, Zehravi Mehrukh, Sweilam Sherouk Hussein, Durgawale Trupti Pratik, Qureshi Mohammad Shamim, Durgapal Sumit, Haque M Akiful, Vodeti Rajeshwar, Urs Deepadarshan, Shatu Mst Maharunnasa, Rab Safia Obaidur, Doukani Koula, Emran Talha Bin
Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka, 1216, Bangladesh.
Laboratory of Agrobiotechnology and Nutrition in Semi-Arid Zones, Faculty of Nature and Life Sciences, University of Ibn Khaldoun, Tiaret, Algeria.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 26. doi: 10.1007/s00210-025-04050-w.
Programmed necrosis, a controlled cell death method that bypasses resistance mechanisms that render apoptosis ineffective, is a potential cancer treatment target. Due to their diverse biological activities and low side effects, natural products are being explored as modulators of programmed necrosis pathways. This review highlights the potential of natural compounds to target cancer cells while preserving healthy tissues and their interaction with essential programmed necrosis mechanisms like ferroptosis and necroptosis. Recent developments have identified various types of programmable necrosis, including necroptosis, ferroptosis, pyroptosis, proptosis, mitochondrial permeability transition-driven necrosis, and oncosis. Natural compounds are increasingly being utilized as a primary source of anti-cancer medications, providing new cancer treatments. This review demonstrates the molecular mechanisms behind lipid peroxidation, mixed lineage kinase domain-like protein, and receptor-interacting protein kinases (RIPK1 and RIPK3) inducing cell death. Recent research has identified natural compounds like polyphenols, alkaloids, and terpenoids that can modulate pathways and benefit preclinical cancer models. The review underscores the potential of natural compounds in developing innovative cancer treatments by integrating pharmacology and cellular signaling knowledge. Integrating natural compound studies and programmed necrosis research presents a promising avenue for oncologists to overcome treatment resistance. Natural compounds have shown potential in developing programmed necrosis as a novel cancer treatment approach, enhancing therapeutic effectiveness and minimizing side effects through preclinical research, pharmacology, and molecular biology.
程序性坏死是一种可控的细胞死亡方式，它绕过了使凋亡无效的抗性机制，是一种潜在的癌症治疗靶点。由于天然产物具有多样的生物活性和低副作用，它们正被探索作为程序性坏死途径的调节剂。本综述强调了天然化合物在靶向癌细胞同时保护健康组织方面的潜力，以及它们与铁死亡和坏死性凋亡等重要程序性坏死机制的相互作用。最近的进展已经确定了各种类型的程序性坏死，包括坏死性凋亡、铁死亡、焦亡、亲死亡、线粒体通透性转换驱动的坏死和胀亡。天然化合物越来越多地被用作抗癌药物的主要来源，提供了新的癌症治疗方法。本综述阐述了脂质过氧化、混合谱系激酶结构域样蛋白以及受体相互作用蛋白激酶（RIPK1和RIPK3）诱导细胞死亡背后的分子机制。最近的研究已经确定了多酚、生物碱和萜类等天然化合物，它们可以调节相关途径并使临床前癌症模型受益。该综述强调了通过整合药理学和细胞信号知识，天然化合物在开发创新癌症治疗方法方面的潜力。将天然化合物研究与程序性坏死研究相结合，为肿瘤学家克服治疗抗性提供了一条有前景的途径。天然化合物在将程序性坏死发展为一种新型癌症治疗方法方面已显示出潜力，通过临床前研究、药理学和分子生物学提高治疗效果并最大限度地减少副作用。
