N-acetyl-L-cysteine enhances chemotherapeutic effect on prostate cancer cells.

Abstract

Transcription factor nuclear factor kappaB (NF-kappaB) controls gene expression of a number of genes, including cytokines such as interleukin-6 (IL-6), granulocyte-macrophage (GM)-CSF, and interleukin-8 (IL-8). IL-6 is known to play important roles in the growth of prostate cancer cells, activation of androgen receptor, and prostate-specific protein expression. NF-kappaB is activated by extracellular signals such as proinflammatory cytokines, chemotherapeutic reagents, and radiation. Here we demonstrate that cisplatin (CDDP) and etoposide (VP-16) induce nuclear translocation of NF-kappaB in prostate cancer cell lines, followed by secretion of IL-6. We also demonstrated that the growth of hormone-independent prostate cancer cell lines can be inhibited by the anti-NF-kappaB reagent N-acetyl-L-cysteine (NAC). These observations indicate that NF-kappaB can be a target of new adjuvant therapy against hormone refractory prostate cancer.