title: FIP-gts potentiate autophagic cell death against cisplatin-resistant urothelial cancer cells.
abstract: BACKGROUND
  Urothelial cancer (UC) is a common cancer among males. Once metastatic or chemoresistant diseases develop, there is little effective treatment available. A fungal immunomodulatory protein, ganoderma tsugae (FIP-gts) possesses antitumor activity against solid tumors and inhibits telomerase activity. FIP-gts induces autophagy in cancer cells and may provide an alternative pathway against chemo-resistance.
  
  
  METHODS
  Two UC cell lines were used to investigate the cytotoxicity effects and the autophagy regulation of FIP-gts using flow cytometry, acidic vesicular organelles (AVO) staining and western blotting.
  
  
  RESULTS
  MTT assay showed that FIP-gts and bafilomycin-A1 (Baf-A1) and or chloroquine (CQ) could enhance a significantly synergistic cytotoxicity. The treatment of UC cell lines with FIP-gts activated LC-3 II formation and AVO positive staining on western blot and flow cytometry. Interestingly, FIP-gts and Baf-A1 combined treatment was found to lead to enhancement of apoptosis along with inhibition of autophagy in parental and resistant UC cells.
  
  
  CONCLUSIONS
  FIP-gts may have the potential to be utilized as a therapeutic adjuvant for the treatment of resistant UC cancer down-regulating Beclin-1 to activate autophagic cell death.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Jian-Ri
authors.initials: JR
authors.lastname: Li
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chen-Li
authors.initials: CL
authors.lastname: Cheng
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Department of Urology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chi-Rei
authors.initials: CR
authors.lastname: Yang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Department of Urology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Yen-Chuan
authors.initials: YC
authors.lastname: Ou
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Wu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Department of Medical Oncology, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. jlko@csmu.edu.tw.
authors.forename: Jiunn-Liang
authors.initials: JL
authors.lastname: Ko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000494:pharmacology*; D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D008297:Male; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents; D005656:Fungal Proteins; D002945:Cisplatin
keywords: Apoptosis; autophagy; chemo-resistant; urothelial carcinoma