Sulfasalazine enhances growth inhibitory activity of doxorubicin: Potential use in combination chemotherapy of advanced prostate cancer

LB-322Advanced prostate cancer is terminal and most deaths from this disease are due to metastases that are highly resistant to conventional therapies, including chemotherapy. There is hence an urgent need for new approaches aimed at overcoming its therapy resistance. Sulfasalazine (SASP) is a drug commonly used for therapy of Crohn’s disease and arthritis. Several groups have shown that it may be useful for therapy of a variety of cancers and a phase I/II trial is ongoing for glioblastoma therapy. We previously showed that SASP can markedly inhibit growth of human DU-145 and PC-3 prostate cancer cells in vitro and in SCID mice. Its growth-inhibitory activity was linked to inhibition of the xc- cystine/glutamate antiporter, a major plasma membrane cystine transporter, leading to cystine starvation and subsequent depletion of glutathione (GSH), a free radical scavenger with a key role in cell maintenance …