{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:02:17Z","timestamp":1790204537574,"version":"4.1.0"},"reference-count":28,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,15]]},"abstract":"<jats:p>ATB0,+ [SLC6A14 (solute carrier family 6 member 14)] is an Na+\/Cl\u2212-coupled amino acid transporter whose expression is upregulated in cancer. 1-Methyltryptophan is an inducer of immune surveillance against tumour cells through its ability to inhibit indoleamine dioxygenase. In the present study, we investigated the role of ATB0,+ in the uptake of 1-methyltryptophan as a potential mechanism for entry of this putative anticancer drug into tumour cells. These studies show that 1-methyltryptophan is a transportable substrate for ATB0,+. The transport process is Na+\/Cl\u2212-dependent with an Na+\/Cl\u2212\/1-methyltryptophan stoichiometry of 2:1:1. Evaluation of other derivatives of tryptophan has led to identification of \u03b1-methyltryptophan as a blocker, not a transportable substrate, for ATB0,+. ATB0,+ can transport 18 of the 20 proteinogenic amino acids. \u03b1-Methyltryptophan blocks the transport function of ATB0,+ with an IC50 value of \u223c250\u00a0\u03bcM under conditions simulating normal plasma concentrations of all these 18 amino acids. These results suggest that \u03b1-methyltryptophan may induce amino acid deprivation in cells which depend on the transporter for their amino acid nutrition. Screening of several mammary epithelial cell lines shows that ATB0,+ is expressed robustly in some cancer cell lines, but not in all; in contrast, non-malignant cell lines do not express the transporter. Treatment of ATB0,+-positive tumour cells with \u03b1-methyltryptophan leads to suppression of their colony-forming ability, whereas ATB0,+-negative cell lines are not affected. The blockade of ATB0,+ in these cells with \u03b1-methyltryptophan is associated with cell cycle arrest. These studies reveal the potential of ATB0,+ as a drug target for cancer chemotherapy.<\/jats:p>","DOI":"10.1042\/bj20080622","type":"journal-article","created":{"date-parts":[[2008,6,11]],"date-time":"2008-06-11T13:31:52Z","timestamp":1213191112000},"page":"343-355","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Interaction of tryptophan derivatives with SLC6A14 (ATB0,+) reveals the potential of the transporter as a drug target for cancer chemotherapy"],"prefix":"10.1042","volume":"414","author":[{"given":"Senthil","family":"Karunakaran","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagavedi\u00a0S.","family":"Umapathy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthusamy","family":"Thangaraju","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Itagaki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u00a0H.","family":"Munn","sequence":"additional","affiliation":[{"name":"Immunotherapy Center, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puttur\u00a0D.","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadivel","family":"Ganapathy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2008,8,27]]},"reference":[{"key":"2021112215041159900_B1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrc1929","article-title":"Targeting the mechanisms of tumoral immune tolerance with small molecule inhibitors","volume":"6","author":"Muller","year":"2006","journal-title":"Nat. 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