Downregulation of Cystine Transporter x(c)(-) by Irinotecan in Human Head and Neck Cancer FaDu Xenografts

Sreenivasulu Chintala; Karoly Toth; Ming-Biao Yin; Arup Bhattacharya; Sylvia B. Smith; M. Shamsul Ola; Shousong Cao; Farukh A. Durrani; Tanjima R. Zinia; Rebecca Dean; Harry K. Slocum; Youcef M. Rustum

doi:10.1159/000316334

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Downregulation of Cystine Transporter x(c)(-) by Irinotecan in Human Head and Neck Cancer FaDu Xenografts

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Downregulation of Cystine Transporter x(c)(-) by Irinotecan in Human Head and Neck Cancer FaDu Xenografts

Sreenivasulu Chintala, Karoly Toth, Ming-Biao Yin, Arup Bhattacharya, Sylvia B. Smith, M. Shamsul Ola, Shousong Cao, Farukh A. Durrani, Tanjima R. Zinia, Rebecca Dean, …

Chemotherapy (Basel), Vol.56(3), pp.223-233

01/01/2010

DOI: 10.1159/000316334

PMCID: PMC2914432

PMID: 20551639

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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. Conclusion: 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. Copyright (C) 2010 S. Karger AG, Basel

Oncology

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

Details

Title: Subtitle: Downregulation of Cystine Transporter x(c)(-) by Irinotecan in Human Head and Neck Cancer FaDu Xenografts
Creators: Sreenivasulu Chintala - Roswell Park Cancer Institute
Karoly Toth - Roswell Park Cancer Institute
Ming-Biao Yin - Roswell Park Cancer Institute
Arup Bhattacharya - Roswell Park Cancer Institute
Sylvia B. Smith - Augusta University
M. Shamsul Ola - Augusta University
Shousong Cao - Roswell Park Cancer Institute
Farukh A. Durrani - Roswell Park Cancer Institute
Tanjima R. Zinia - Roswell Park Cancer Institute
Rebecca Dean - Roswell Park Cancer Institute
Harry K. Slocum - Roswell Park Cancer Institute
Youcef M. Rustum - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: Chemotherapy (Basel), Vol.56(3), pp.223-233
Publisher: Karger
DOI: 10.1159/000316334
PMID: 20551639
PMCID: PMC2914432
ISSN: 0009-3157
eISSN: 1421-9794
Number of pages: 11
Grant note: R01EY014560 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) CA 16056 / National Cancer Institute, Bethesda, Md., USA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA016056 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
Language: English
Date published: 01/01/2010
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359892702771

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