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生物学和药物化学方法在各种凋亡诱导剂中的应用。

Biology and medicinal chemistry approaches towards various apoptosis inducers.

机构信息

Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, S.G. Highway, Charodi, Ahmedabad 382 481, Gujarat, India.

出版信息

Anticancer Agents Med Chem. 2013 Mar;13(3):433-55. doi: 10.2174/1871520611313030007.

Abstract

Apoptosis is a genetically in-built process whereby organisms remove unwanted cells. Apoptosis can serve as a regulatory and defense mechanism in the formation of the shape and size of the human body and also to eradicate surplus amount of cells. The regulation of apoptosis is relevant and differentiates between a normal cells of body and cancer cells by loss of control. Apoptosis being an intricate process regulated by much more than just a biological mechanism. The induction of the apoptosis manifests the control on the tumour size and number of tumour cells hence establishing the application of apoptotic inducers as vital components in the treatment of cancer. During apoptosis, cells die in a controlled and regulated fashion which makes apoptosis distinct from necrosis (uncontrolled cell death). Protein components and regulators for apoptosis signaling pathways can involve the mitochondria (intrinsic pathway) or signal through death receptors (extrinsic pathway). Many different drug and gene therapy approaches are being tested for initiating apoptosis. Resistance to apoptosis is considered a hallmark of cancer. Therapeutic approaches attempted to date include traditional small molecules, antisense oligonucleotides, monoclonal antibodies, recombinant proteins and several classes of chemical compounds discussed in this review. These compounds may serve as precursor molecules for more effective drugs, all aimed at developing clinically effective therapeutics, targeting key apoptosis regulatory mechanism. This review will discuss the current understanding of apoptosis induced by various chemical agents and highlighting the role of apoptosis inducing agents as emerging opportunities for cancer therapy.

摘要

细胞凋亡是一种由基因控制的细胞程序性死亡过程,生物体借此清除不需要的细胞。细胞凋亡可以作为一种调节和防御机制,有助于维持人体的形态和大小,并清除多余的细胞。细胞凋亡的调节在区分正常细胞和癌细胞方面具有重要意义,正常细胞的凋亡受到控制,而癌细胞则失去控制。细胞凋亡是一个复杂的过程,受到的调控远不止生物学机制。细胞凋亡的诱导可以控制肿瘤的大小和肿瘤细胞的数量,因此将凋亡诱导剂作为癌症治疗的重要组成部分具有重要的应用价值。在细胞凋亡过程中,细胞以受控和可调节的方式死亡,这使其与坏死(不受控制的细胞死亡)区分开来。参与细胞凋亡信号通路的蛋白成分和调节剂可以涉及线粒体(内在途径)或通过死亡受体(外在途径)信号传递。目前正在测试许多不同的药物和基因治疗方法来诱导细胞凋亡。对细胞凋亡的抵抗被认为是癌症的一个标志。迄今为止尝试的治疗方法包括传统的小分子、反义寡核苷酸、单克隆抗体、重组蛋白和本综述中讨论的几类化学化合物。这些化合物可以作为更有效药物的前体分子,所有这些都旨在开发针对关键细胞凋亡调节机制的临床有效治疗方法。本文综述了各种化学试剂诱导细胞凋亡的最新研究进展,并强调了细胞凋亡诱导剂作为癌症治疗新策略的潜力。

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