We are analyzing https://link.springer.com/article/10.1007/s00280-008-0894-4.

Title:
The x c − cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine | Cancer Chemotherapy and Pharmacology
Description:
To determine whether the x c − cystine transporter could be a useful therapeutic target for small-cell lung cancer (SCLC). Human SCLC cell cultures were examined for growth dependence on extracellular cystine, x c − expression, glutathione levels and response to highly specific x c − inhibitors, i.e., monosodium glutamate (MSG) and the anti-inflammatory drug, sulfasalazine (SASP). In studying tumor growth inhibition by SASP, use was also made of a novel SCLC tissue xenograft model, LU6-SCLC, derived from a chemoresistant patient’s SCLC specimen. Growth of NCI-H69 and NCI-H82 SCLC cells greatly depended on x c − -mediated uptake of cystine. SASP substantially reduced their glutathione levels (>70%; 0.3 mM SASP; 24 h) and growth (72 h) with IC50s of 0.21 and 0.13 mM, respectively; MSG also inhibited growth markedly. Both SASP- and MSG-induced growth arrests were largely prevented by cystine uptake-enhancing 2-mercaptoethanol (66 μM) indicating they were primarily due to cystine starvation. Without major side-effects, SASP (i.p.) restrained growth of NCI-H69 cell xenografts (~50%) and, importantly, substantially inhibited growth of the clinically more relevant LU6-SCLC tissue xenografts (~70% by stereological analysis), reducing tumor glutathione contents. The x c − cystine/glutamate antiporter is potentially useful as a target for therapy of SCLC based on glutathione depletion. Sulfasalazine may be readily used for this approach, especially in combination chemotherapy.
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article, cancer, google, scholar, pubmed, cas, cystine, growth, gout, sulfasalazine, wang, cells, lung, research, buckley, cell, glutathione, human, drug, tumor, sclc, canada, cystineglutamate, target, smallcell, sasp, therapy, prostate, clin, department, privacy, cookies, content, chemotherapy, antiporter, potential, peter, yuzhuo, depletion, access, res, ireland, vancouver, university, publish, search, guan, dockery, transporter, levels,

Topics {✒️}

small-cell lung cancer month download article/chapter yu-zhuo wang molecularly targeted therapies cystine-glutamate transporter slc7a11 studying tumor progression-related nci-h69 cell xenografts arsenic-resistant cell lines antigen-presenting cells control article cancer chemotherapy sulfasalazine-induced cystine starvation lymphoma growth-inhibitory activity transplantable tumor lines cystine uptake-enhancing 2-mercaptoethanol msg-induced growth arrests sulfasalazine inhibits proliferation full article pdf author information authors nuclear factor kappa human xenograft cancer drug development tumor infiltrating cd8+ van venrooij wj privacy choices/manage cookies anti-inflammatory drug vitro cell line sulfasalazine-induced reduction prostate cancer therapy cystine transporter breast cancer cells mammalian glutathione synthesis related subjects cell growth inhibition growth-inhibitory activity prostate cancer cells pancreatic cancer cells subrenal capsule xenografts lung cancer national cancer institute cystine uptake disrupts pancreatic cancer growth anti-cancer effect cystine/glutamate antiporter mediated uptake amino acid transporters primary brain tumors nb2 lymphoma cells engineering research council van lent pl potential therapeutic target

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         headline:The x c − cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine
         description:To determine whether the x c − cystine transporter could be a useful therapeutic target for small-cell lung cancer (SCLC). Human SCLC cell cultures were examined for growth dependence on extracellular cystine, x c − expression, glutathione levels and response to highly specific x c − inhibitors, i.e., monosodium glutamate (MSG) and the anti-inflammatory drug, sulfasalazine (SASP). In studying tumor growth inhibition by SASP, use was also made of a novel SCLC tissue xenograft model, LU6-SCLC, derived from a chemoresistant patient’s SCLC specimen. Growth of NCI-H69 and NCI-H82 SCLC cells greatly depended on x c − -mediated uptake of cystine. SASP substantially reduced their glutathione levels (>70%; 0.3 mM SASP; 24 h) and growth (72 h) with IC50s of 0.21 and 0.13 mM, respectively; MSG also inhibited growth markedly. Both SASP- and MSG-induced growth arrests were largely prevented by cystine uptake-enhancing 2-mercaptoethanol (66 μM) indicating they were primarily due to cystine starvation. Without major side-effects, SASP (i.p.) restrained growth of NCI-H69 cell xenografts (~50%) and, importantly, substantially inhibited growth of the clinically more relevant LU6-SCLC tissue xenografts (~70% by stereological analysis), reducing tumor glutathione contents. The x c − cystine/glutamate antiporter is potentially useful as a target for therapy of SCLC based on glutathione depletion. Sulfasalazine may be readily used for this approach, especially in combination chemotherapy.
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            Glutathione
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            Pharmacology/Toxicology
            Cancer Research
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      headline:The x c − cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine
      description:To determine whether the x c − cystine transporter could be a useful therapeutic target for small-cell lung cancer (SCLC). Human SCLC cell cultures were examined for growth dependence on extracellular cystine, x c − expression, glutathione levels and response to highly specific x c − inhibitors, i.e., monosodium glutamate (MSG) and the anti-inflammatory drug, sulfasalazine (SASP). In studying tumor growth inhibition by SASP, use was also made of a novel SCLC tissue xenograft model, LU6-SCLC, derived from a chemoresistant patient’s SCLC specimen. Growth of NCI-H69 and NCI-H82 SCLC cells greatly depended on x c − -mediated uptake of cystine. SASP substantially reduced their glutathione levels (>70%; 0.3 mM SASP; 24 h) and growth (72 h) with IC50s of 0.21 and 0.13 mM, respectively; MSG also inhibited growth markedly. Both SASP- and MSG-induced growth arrests were largely prevented by cystine uptake-enhancing 2-mercaptoethanol (66 μM) indicating they were primarily due to cystine starvation. Without major side-effects, SASP (i.p.) restrained growth of NCI-H69 cell xenografts (~50%) and, importantly, substantially inhibited growth of the clinically more relevant LU6-SCLC tissue xenografts (~70% by stereological analysis), reducing tumor glutathione contents. The x c − cystine/glutamate antiporter is potentially useful as a target for therapy of SCLC based on glutathione depletion. Sulfasalazine may be readily used for this approach, especially in combination chemotherapy.
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         SCLC xenograft model
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         Pharmacology/Toxicology
         Cancer Research
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      name:Department of Surgery, National University of Ireland, Galway, Ireland
      name:Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, USA
      name:James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, USA
      name:Department of Cancer Imaging, BC Cancer Agency, Research Centre, Vancouver, Canada
      name:Department of Cancer Endocrinology, BC Cancer Agency, Research Centre, Vancouver, Canada
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