• Daniel W Doxsee, Peter W Gout, Takeshi Kurita, Maisie Lo, Arthur R Buckley, Yuwei Wang, Hui Xue, Cristina M Karp, Jean-Claude Cutz, Gerald R Cunha, and Yu-Zhuo Wang.
• Department of Cancer Endocrinology, BC Cancer Agency, Vancouver, British Columbia, Canada.
• Prostate. 2007 Feb 1;67(2):162-71.

BackgroundCertain cancers depend for growth on uptake of cystine/cysteine from their environment. Here we examined advanced human prostate cancer cell lines, DU-145 and PC-3, for dependence on extracellular cystine and sensitivity to sulfasalazine (SASP), a potent inhibitor of the x(c)(-) cystine transporter.MethodsCultures were evaluated for growth dependence on exogenous cystine, x(c)(-) transporter expression, response to SASP (growth and glutathione content). In vivo, effect of SASP was determined on subrenal capsule xenograft growth.ResultsCystine omission from culture medium arrested DU-145 and PC-3 cell proliferation; both cell lines expressed the x(c)(-) transporter and were growth inhibited by SASP (IC(50)s: 0.20 and 0.28 mM, respectively). SASP-induced growth inhibition was associated with vast reductions in cellular glutathione content - both effects based on cystine starvation. SASP (i.p.) markedly inhibited growth of DU-145 and PC-3 xenografts without major toxicity to hosts.ConclusionsSASP-induced cystine/cysteine starvation leading to glutathione depletion may be useful for therapy of prostate cancers dependent on extracellular cystine.(c) 2006 Wiley-Liss, Inc.

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