Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24 human bladder cancer cells.
BACKGROUND
MMPs play a crucial role in the process of cancer invasion and metastasis.


METHODS
The influence of NAC on invasion and MMP-9 production of human bladder cancer cell line T24 was investigated using an in vitro invasion assay, gelatin zymography, Western and Northern blot analyses and RT-PCR assays.


RESULTS
TPA increased the number of invading T24 cells through reconstituted basement membrane more than 10-fold compared to basal condition. NAC inhibited TPA-enhanced invasion dose-dependently. TPA increased the MMP-9 production by T24 cells without altering expression of TIMP-1 gene, while NAC suppressed TPA-enhanced production of MMP-9. Neither TPA nor NAC altered TIMP-1 mRNA level in T24 cells. In vitro experiments demonstrated that MMP-9 was directly inhibited by NAC but was not influenced by TPA.


CONCLUSIONS
NAC limits invasion of T24 human bladder cancer cells by inhibiting the MMP-9 production in addition to a direct inhibition of MMP-9 activity.
Kawakami
S
S
Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan. s-kawakami@med.tmd.ac.jp
Kageyama
Y
Y
Fujii
Y
Y
Kihara
K
K
Oshima
H
H
D000111:Acetylcysteine / Q000494:pharmacology*; D001485:Basement Membrane / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine