title: Inhibition of autophagy promotes apoptosis and enhances anticancer efficacy of adriamycin via augmented ROS generation in prostate cancer cells.
abstract: The interplay between autophagy and apoptosis response to chemotherapy is still a subject of intense debate in recent years. More efforts have focused on the regulation effects of apoptosis on autophagy, whereas how autophagy affects apoptosis remains poorly understood. In this study performed on prostate cancer cells, we investigated the role of autophagy in adriamycin-induced apoptosis, as well as the mechanisms mediating the effects of autophagy on apoptosis response to adriamycin (ADM). The results show that ADM not only inhibited cell viability and enhanced apoptosis, but also promoted autophagy via PI3K/Akt(T308)/mTOR signal pathway. Inhibition of autophagy by either pharmacological inhibitor chloroquine (CQ) or RNA interference of Atg5 increased ADM-induced apoptosis and enhanced the chemosensitivity of prostate cancer cells. Moreover, blockade of autophagy augmented reactive oxygen species (ROS) generation induced by ADM. Scavenging of ROS by antioxidant N-acetyl-cysteine (NAC) reversed the strengthened effects of CQ on ADM-induced apoptosis and rescued the cells from apoptosis. The results identified ROS as a potential mediator directing the modulation effects of the protective autophagy on apoptosis response to ADM. Suppression of the protective autophagy might provide a promising strategy to increase the anticancer efficacy of agents in the treatment of prostate cancer.
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Tan
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Cell biology, Jinan University, Guangzhou 510632, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Luo
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaomian
authors.initials: X
authors.lastname: Lin
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Jialong
authors.initials: J
authors.lastname: Cai
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, and Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou 510632, China; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: twxp@jnu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases
keywords: Apoptosis; Autophagy; Prostate cancer; Reactive oxygen species