Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy.
Cells. 2022 Apr 4;11(7):1221. doi: 10.3390/cells11071221.
Necroptosis is a programmed form of necrosis characterized by mitochondrial alterations and plasma membrane permeabilization resulting in the release of cytoplasmic content into extracellular space, and leading to inflammatory reactions. Besides its critical role in viral defense mechanisms and inflammatory diseases, necroptosis plays pivotal functions in the drug response of tumors, including prostate cancer. Necroptosis is mainly governed by kinase enzymes, including RIP1, RIP3, and MLKL, and conversely to apoptosis, is a caspase-independent mechanism of cell death. Numerous compounds induce necroptosis in prostate cancer models, including (i) compounds of natural origin, (ii) synthetic and semisynthetic small molecules, and (iii) selenium and selenium-based nanoparticles. Here, we overview the molecular mechanisms underlying necroptosis and discuss the possible implications of drugs inducing necroptosis for prostate cancer therapy.
细胞程序性坏死是一种坏死形式，其特征为线粒体改变和质膜通透性增加，导致细胞质内容物释放到细胞外空间，并引发炎症反应。除了在病毒防御机制和炎症性疾病中具有关键作用外，细胞程序性坏死在肿瘤的药物反应中也起着关键作用，包括前列腺癌。细胞程序性坏死主要受激酶酶的调控，包括 RIP1、RIP3 和 MLKL，与细胞凋亡相反，是一种 caspase 非依赖性的细胞死亡机制。许多化合物在前列腺癌模型中诱导细胞程序性坏死，包括（i）天然来源的化合物，（ii）合成和半合成小分子，以及（iii）硒和基于硒的纳米颗粒。在这里，我们综述了细胞程序性坏死的分子机制，并讨论了诱导细胞程序性坏死的药物对前列腺癌治疗的可能影响。
