D-glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K.
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.
Oh
Hyun-Ji
HJ
Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Daegu 700-712, Republic of Korea.
Lee
Jason S
JS
Song
Dae-Kyu
DK
Shin
Dong-Hoon
DH
Jang
Byeong-Churl
BC
Suh
Seong-Il
SI
Park
Jong-Wook
JW
Suh
Min-Ho
MH
Baek
Won-Ki
WK
D049109:Cell Proliferation / Q000187:drug effects*; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors*; D020123:Sirolimus / Q000494:pharmacology
D038762:Ribosomal Protein S6 Kinases, 70-kDa; D005944:Glucosamine; D020123:Sirolimus