Adenylate kinase 3 sensitizes cells to cigarette smoke condensate vapor induced cisplatin resistance

Xiaofei Chang, Rajani Ravi, Vui Pham, Atul Bedi, Aditi Chatterjee, David Sidransky

Research output: Contribution to journalArticle

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. Methodology/Principal Findings: 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/Significance: The current study provides evidence that chronic CSC vapor exposure affects AK3 expression and renders the cells resistant to cisplatin.

Original languageEnglish (US)
Article numbere20806
JournalPloS one
Volume6
Issue number6
DOIs
StatePublished - Jun 20 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Adenylate kinase 3 sensitizes cells to cigarette smoke condensate vapor induced cisplatin resistance'. Together they form a unique fingerprint.

  • Cite this