title: Downregulation of cystine transporter xc by irinotecan in human head and neck cancer FaDu xenografts.
abstract: BACKGROUND
  The purpose of this study was: (1) to document the critical requirement of cystine for growth of human tumor cells in vitro, and (2) to determine the effect of the anticancer agent irinotecan on the cystine transporter x(c)(-) in head and neck FaDu xenografts.
  
  
  METHODS
  Cell growth was measured by sulforhodamine B assay. xCT protein, glutathione (GSH) and DNA damage were determined using Western blot, spectrophotometry, and immunohistochemistry, respectively.
  
  
  RESULTS
  Depletion of cystine from the medium inhibited tumor cell growth. Treatment of FaDu tumor with a therapeutic dose of irinotecan resulted in depression of xCT protein levels, leading to tumor growth retardation and downregulation of GSH with increased reactive oxygen species (ROS). The accumulation of ROS correlated with increased DNA damage as evidenced by increased H2AX.
  
  
  CONCLUSIONS
  Depression of xCT protein by irinotecan resulted in downregulation of GSH and increase in ROS, which could be the other possible mechanisms of DNA damage by irinotecan.
authors.affiliation: Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. sreenivasulu.chintala@roswellpark.org
authors.forename: Sreenivasulu
authors.initials: S
authors.lastname: Chintala
authors.forename: Károly
authors.initials: K
authors.lastname: Tóth
authors.forename: Ming-Biao
authors.initials: MB
authors.lastname: Yin
authors.forename: Arup
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Sylvia B
authors.initials: SB
authors.lastname: Smith
authors.forename: M Shamsul
authors.initials: MS
authors.lastname: Ola
authors.forename: Shousong
authors.initials: S
authors.lastname: Cao
authors.forename: Farukh A
authors.initials: FA
authors.lastname: Durrani
authors.forename: Tanjima R
authors.initials: TR
authors.lastname: Zinia
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dean
authors.forename: Harry K
authors.initials: HK
authors.lastname: Slocum
authors.forename: Youcef M
authors.initials: YM
authors.lastname: Rustum
mesh_terms: D026905:Amino Acid Transport Systems / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003553:Cystine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D026905:Amino Acid Transport Systems; D003553:Cystine; D000077146:Irinotecan; D002166:Camptothecin