College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
Biomol Ther (Seoul). 2014 May;22(3):167-75. doi: 10.4062/biomolther.2014.046.
Chemotherapy has long been considered as one of useful strategies for cancer treatment. It is primarily based on the apoptosis that can selectively kill cancer cells. However, cancer cells can progressively develop an acquired resistance to apoptotic cell death, rendering refractory to chemo- and radiotherapies. Although the mechanism by which cells attained resistance to drug remains to be clarified, it might be caused by either pumping out of them or interfering with apoptotic signal cascades in response to cancer drugs. In case that cancer cells are defective in some part of apoptotic machinery by repeated exposure to anticancer drugs, alternative cell death mechanistically distinct from apoptosis could be adopted to remove cancer cells refractory to apoptosis-inducing agents. This review will mainly deal with harnessing of necrotic cell death, specifically, programmed necrosis and practical uses. Here, we begin with various defects of apoptotic death machinery in cancer cells, and then provide new perspective on programmed necrosis as an alternative anticancer approach.
化疗长期以来被认为是癌症治疗的一种有效策略。它主要基于细胞凋亡,可选择性地杀死癌细胞。然而,癌细胞会逐渐对细胞凋亡产生获得性耐药性,从而对化疗和放疗产生耐药性。虽然细胞获得耐药性的机制仍有待阐明,但这可能是由于细胞将药物泵出或干扰对癌症药物的凋亡信号级联反应所致。如果癌细胞由于反复接触抗癌药物而在凋亡机制的某些部分存在缺陷,则可以采用与凋亡不同的机制的另一种细胞死亡方式来清除对凋亡诱导剂产生耐药性的癌细胞。本综述将主要探讨坏死性细胞死亡,特别是程序性细胞坏死的利用和实际用途。在这里,我们首先讨论癌细胞中凋亡死亡机制的各种缺陷,然后为程序性坏死作为一种替代的抗癌方法提供新的视角。