Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP 91501-970 Porto Alegre, RS, Brazil.
Departamento de Ciências Básicas da Saúde, Bioquímica, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite 245/201 Anexo II, CEP 90050-170 Porto Alegre, RS, Brazil.
Mutat Res. 2013 Oct-Dec;753(2):91-99. doi: 10.1016/j.mrrev.2013.07.001. Epub 2013 Jul 18.
Many alkylating agents are used as chemotherapeutic drugs and have a long history of clinical application. These agents inflict a wide range of DNA damage resulting in a complex cellular response. After DNA damage, cells trigger a series of signaling cascades promoting cellular survival and cell cycle blockage which enables time for DNA repair to occur. More recently, induction of autophagy has been observed in cancer cells after treatment with different DNA-targeted anticancer drugs, including alkylating agents. Several studies have demonstrated that induction of autophagy after DNA damage delays apoptotic cell death and may therefore lead to chemoresistance, which is the limiting factor for successful chemotherapy. On the other hand, depending on the extent of damage and the cellular context, the induction of autophagy may also contribute to cell death. Given these conflicting results, many studies have been conducted to better define the role of autophagy in cancer cells in response to chemotherapy. In this review, we describe the main alkylating agents used in clinical oncology as well as the cellular response they evoke with emphasis on autophagy.
许多烷化剂被用作化疗药物，具有长期的临床应用历史。这些试剂会造成广泛的 DNA 损伤，导致复杂的细胞反应。在 DNA 损伤后，细胞会触发一系列信号级联反应，促进细胞存活和细胞周期阻滞，从而为 DNA 修复提供时间。最近，在使用不同的靶向 DNA 的抗癌药物（包括烷化剂）治疗癌细胞后，观察到自噬的诱导。几项研究表明，DNA 损伤后自噬的诱导会延迟细胞凋亡死亡，因此可能导致化疗耐药，这是化疗成功的限制因素。另一方面，根据损伤的程度和细胞环境，自噬的诱导也可能有助于细胞死亡。鉴于这些相互矛盾的结果，许多研究已经进行，以更好地定义自噬在化疗药物诱导的癌细胞中的作用。在这篇综述中，我们描述了临床肿瘤学中使用的主要烷化剂以及它们引起的细胞反应，重点是自噬。
