N-acetyl-L-cysteine enhances chemotherapeutic effect on prostate cancer cells.
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.
Tozawa
Keiichi
K
Department of Urology, Nagoya City University Medical School, Nagoya, Japan. toza@med.nagoya-cu.ac.jp
Okamoto
Takashi
T
Hayashi
Yutaro
Y
Sasaki
Shoichi
S
Kawai
Noriyasu
N
Kohri
Kenjiro
K
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015850:Interleukin-6; D016328:NF-kappa B; D005047:Etoposide; D002945:Cisplatin; D000111:Acetylcysteine