title: Adenylate kinase 3 sensitizes cells to cigarette smoke condensate vapor induced cisplatin resistance.
abstract: BACKGROUND
  The major established etiologic risk factor for bladder cancer is cigarette smoking and one of the major antineoplastic agents used for the treatment of advanced bladder cancer is cisplatin. A number of reports have suggested that cancer patients who smoke while receiving treatment have lower rates of response and decreased efficacy of cancer therapies.
  
  
  RESULTS
  In this study, we investigated the effect of cigarette smoke condensate (CSC) vapor on cisplatin toxicity in urothelial cell lines SV-HUC-1 and SCaBER cells. We showed that chronic exposure to CSC vapor induced cisplatin resistance in both cell lines. In addition, we found that the expression of mitochondrial-resident protein adenylate kinase-3 (AK3) is decreased by CSC vapor. We further observed that chronic CSC vapor-exposed cells displayed decreased cellular sensitivity to cisplatin, decreased mitochondrial membrane potential (ΔΨm) and increased basal cellular ROS levels compared to unexposed cells. Re-expression of AK3 in CSC vapor-exposed cells restored cellular sensitivity to cisplatin. Finally, CSC vapor increased the growth of the tumors and also curtail the response of tumor cells to cisplatin chemotherapy in vivo.
  
  
  CONCLUSIONS
  The current study provides evidence that chronic CSC vapor exposure affects AK3 expression and renders the cells resistant to cisplatin.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chang
authors.forename: Rajani
authors.initials: R
authors.lastname: Ravi
authors.forename: Vui
authors.initials: V
authors.lastname: Pham
authors.forename: Atul
authors.initials: A
authors.lastname: Bedi
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D012906:Smoke; D014026:Nicotiana
chemical_list: D000970:Antineoplastic Agents; D012906:Smoke; D000263:Adenylate Kinase; D002945:Cisplatin