D-Glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K

Abstract

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 p70S6 K 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.

Keywords d-Glucosamine; p70S6K; RPS6; Cell proliferation; Prostate cancer; Breast cancer