title: Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells.
abstract: The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2. Rad001 and ATO also can synergistically inhibit tumors in prostate cancer xenograft animal model. These results identify and validate a novel mechanism to enhance and expand the existing targeted therapeutic agent to treat prostate cancer.
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tai
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Lingfan
authors.initials: L
authors.lastname: Xu
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Kaipin
authors.initials: K
authors.lastname: Zhang
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Department of Urology, The First Affiliated Hospital of Anhui Medical University, China.|The Department of Urology, The Urological Institute of Anhui Medical University, China.
authors.forename: Chaozhao
authors.initials: C
authors.lastname: Liang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004357:Drug Synergism; D000068338:Everolimus / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008297:Male; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010087:Oxides; D000068338:Everolimus; D000077237:Arsenic Trioxide
keywords: ATO; Rad001; autophagy; prostate cancer; synergism