title: DNA alkylation damage and autophagy induction.
abstract: 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.
authors.affiliation: Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP 91501-970 Porto Alegre, RS, Brazil.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Bordin
authors.affiliation: Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP 91501-970 Porto Alegre, RS, Brazil.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lima
authors.affiliation: Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP 91501-970 Porto Alegre, RS, Brazil.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.affiliation: 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.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH Surrey, UK.
authors.forename: Lisiane B
authors.initials: LB
authors.lastname: Meira
authors.affiliation: Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris 75571, France; Institut National de la Santé et de la Recherche Médicale U938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Mésange
authors.affiliation: Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris 75571, France; Institut National de la Santé et de la Recherche Médicale U938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Soares
authors.affiliation: Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris 75571, France; Institut National de la Santé et de la Recherche Médicale U938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Annette K
authors.initials: AK
authors.lastname: Larsen
authors.affiliation: Laboratory of Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Paris 75571, France; Institut National de la Santé et de la Recherche Médicale U938, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Escargueil
authors.affiliation: Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP 91501-970 Porto Alegre, RS, Brazil; Instituto de Biotecnologia, Universidade de Caxias do Sul, Rua Francisco Getúlio Vargas, 1130, CEP 95070-560 Caxias do Sul, RS, Brazil. Electronic address: pegas.henriques@gmail.com.
authors.forename: João A P
authors.initials: JAP
authors.lastname: Henriques
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects; D006801:Humans
chemical_list: D000477:Alkylating Agents; D018906:Antineoplastic Agents, Alkylating
keywords: Alkylating agents; Autophagy; DNA damage