BACKGROUND: Malignant progression of lymphoma cells is associated with acquisition of the cystine/glutamate antiporter, xc-, enhancing cystine uptake. Recently, we showed that sulfasalazine (SASP) is a specific xc- inhibitor. Here, we investigated xc- in mammary cancer cell lines. MATERIALS AND METHODS: Expression and function of xc- were evaluated by RT-PCR and 35S-cystine uptake analysis. RESULTS: Xc- expression was elevated 4-fold (p < 0.001) in cells of the most malignant line, MDA-MB-231, associated with increased 35S-cystine uptake (p < 0.001). Proliferation was inhibited by 0.2-0.5 mM SASP. 2-Mercaptoethanol (60 microM), a cystine uptake enhancer, completely prevented SASP-mediated growth inhibition in MDA-MB-231 cultures, but only partially in 184A1 and MCF-7 cultures. SASP-induced growth arrest was reversible and not cell cycle-specific. CONCLUSION: The results suggest: (i) malignant progression of human mammary cancer may be associated with acquisition of xc- expression potentially leading to increased growth autonomy and drug resistance, (ii) xc- may act as a therapeutic target.
BACKGROUND: Malignant progression of lymphoma cells is associated with acquisition of the cystine/glutamate antiporter, xc-, enhancing cystine uptake. Recently, we showed that sulfasalazine (SASP) is a specific xc- inhibitor. Here, we investigated xc- in mammary cancer cell lines. MATERIALS AND METHODS: Expression and function of xc- were evaluated by RT-PCR and 35S-cystine uptake analysis. RESULTS: Xc- expression was elevated 4-fold (p < 0.001) in cells of the most malignant line, MDA-MB-231, associated with increased 35S-cystine uptake (p < 0.001). Proliferation was inhibited by 0.2-0.5 mM SASP. 2-Mercaptoethanol (60 microM), a cystine uptake enhancer, completely prevented SASP-mediated growth inhibition in MDA-MB-231 cultures, but only partially in 184A1 and MCF-7 cultures. SASP-induced growth arrest was reversible and not cell cycle-specific. CONCLUSION: The results suggest: (i) malignant progression of human mammary cancer may be associated with acquisition of xc- expression potentially leading to increased growth autonomy and drug resistance, (ii) xc- may act as a therapeutic target.
Authors: Sreenivasulu Chintala; Károly Tóth; 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 Journal: Chemotherapy Date: 2010-06-11 Impact factor: 2.544
Authors: Jack M Webster; Christine A Morton; Bruce F Johnson; Hua Yang; Michael J Rishel; Brian D Lee; Qing Miao; Chittari Pabba; Donald T Yapp; Paul Schaffer Journal: J Nucl Med Date: 2014-02-27 Impact factor: 10.057
Authors: Kimberly J Briggs; Peppi Koivunen; Shugeng Cao; Keriann M Backus; Benjamin A Olenchock; Hetalben Patel; Qing Zhang; Sabina Signoretti; Gary J Gerfen; Andrea L Richardson; Agnieszka K Witkiewicz; Benjamin F Cravatt; Jon Clardy; William G Kaelin Journal: Cell Date: 2016-06-30 Impact factor: 41.582