N-acetyl cysteine inhibits human signet ring cell gastric cancer cell line (SJ-89) cell growth by inducing apoptosis and DNA synthesis arrest

作者：Li, Jian; Tu, Huai-Jun; Li, Jie; Dai, Ge; Dai, Yu-Cheng; Wu, Qiong; Shi, Qing-Zhi; Cao, Qing; Li, Zhen-Jiang

来源：European Journal of Gastroenterology and Hepatology, 2007, 19(9): 769-774.

DOI：10.1097/MEG.0b013e3282202bda

• apoptosis
• gastric cancer
• N-acetyl cysteine

Background and aims In this study, we investigated the inhibitory effects of N-acetyl cysteine (NAC) on the growth of the human signet ring cell from the gastric-cancer cell line SJ-89, via the induction of apoptosis and the arrest of DNA synthesis.
Materials and methods SJ-89 cells were regularly incubated in the presence of NAC at 5, 10 and 20 mmol/l, and with IMDM as untreated control. Trypan blue-dye exclusion analysis and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay were applied to detect cell proliferation. Apoptotic morphology was observed by electron microscopy. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay were performed to detect NAC-triggered apoptosis.
Results NAC could inhibit proliferation of human gastric cancer SJ-89 cells in a dose-dependent and time-dependent manner. The growth curve showed suppression by 15.8, 37.6 and 66.3% following 72 h of NAC treatment at 5, 10 and 20 mmol/l, respectively, similar to the findings of 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis was evidently reduced by 25, 39 and 91% after 24 h NAC treated at 20 mmol/l and 5 days at 10 and 20 mmol/l, respectively. Cell growth was inhibited by 100% with the treatment of 20 mmol/l NAC on day 6. NAC-treated SJ-89 cells were characterized by typical apoptotic alterations, including morphological changes by electron microscopy, typical apoptotic sub-G, peaking observed by flow cytometry and increase of apoptotic cells with the elevation of the concentration of NAC in a clearly dose-dependent manner by TUNEL assay; Electrophoresis analysis showed typical 'DNA ladder.
Conclusion The data above implicated that NAC inhibits human gastric-cancer SJ-89 cell growth by inducing apoptosis and DNA synthesis arrest. Although the exact mechanisms involved in NAC-induced apoptosis have not been known up to now, the ability to induce apoptosis in a tumor-cell population within 48 h is worth noting. It is also noteworthy that NAC can selectively inhibit the growth of tumor cells. Further studies are needed to elucidate the mechanisms.

• 出版日期2007-9
• 单位南昌大学; 中国人民解放军第九四医院