Oh Hyun-Ji, Lee Jason S, Song Dae-Kyu, Shin Dong-Hoon, Jang Byeong-Churl, Suh Seong-Il, Park Jong-Wook, Suh Min-Ho, Baek Won-Ki
Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Daegu 700-712, Republic of Korea.
Biochem Biophys Res Commun. 2007 Sep 7;360(4):840-5. doi: 10.1016/j.bbrc.2007.06.137. Epub 2007 Jul 5.
Although D-glucosamine has been reported as an inhibitor of tumor growth both in vivo and in vitro, the mechanism for the anticancer effect of D-glucosamine is still unclear. Since there are several reports suggesting D-glucosamine inhibits protein synthesis, we examined whether D-glucosamine affects p70S6K activity, an important signaling molecule involved in protein translation. In the present study, we found D-glucosamine inhibited the activity of p70S6K and the proliferation of DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. D-glucosamine decreased phosphorylation of p70S6K, and its downstream substrates RPS6, and eIF-4B, but not mTOR and 4EBP1 in DU145 cells, suggesting that D-glucosamine induced inhibition of p70S6K is not through the inhibition of mTOR. In addition, D-glucosamine enhanced the growth inhibitory effects of rapamycin, a specific inhibitor of mTOR. These findings suggest that D-glucosamine can inhibit growth of cancer cells through dephosphorylation of p70S6K.
尽管已有报道称D - 葡萄糖胺在体内和体外均为肿瘤生长抑制剂，但D - 葡萄糖胺抗癌作用的机制仍不清楚。由于有几份报告表明D - 葡萄糖胺抑制蛋白质合成，我们研究了D - 葡萄糖胺是否影响p70S6K活性，p70S6K是参与蛋白质翻译的重要信号分子。在本研究中，我们发现D - 葡萄糖胺抑制p70S6K的活性以及DU145前列腺癌细胞和MDA - MB - 231乳腺癌细胞的增殖。D - 葡萄糖胺降低了DU145细胞中p70S6K及其下游底物RPS6和eIF - 4B的磷酸化水平，但未降低mTOR和4EBP1的磷酸化水平，这表明D - 葡萄糖胺诱导的p70S6K抑制不是通过抑制mTOR实现的。此外，D - 葡萄糖胺增强了雷帕霉素（一种mTOR特异性抑制剂）的生长抑制作用。这些发现表明，D - 葡萄糖胺可通过使p70S6K去磷酸化来抑制癌细胞的生长。
