Open Access Highly Accessed Research article

The novel IGF-IR/Akt–dependent anticancer activities of glucosamine

Ki-Hoon Song1, Ju-Hee Kang12, Jong-Kyu Woo5, Jeong-Seok Nam3, Hye-Young Min4, Ho-Young Lee4, Soo-Youl Kim1 and Seung-Hyun Oh56*

Author Affiliations

1 Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea

2 Department of Food and Nutrition, College of Human Ecology, Chung-Ang University, Ansung, Gyeonggi-do, Republic of Korea

3 Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea

4 College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea

5 Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 406-840, Republic of Korea

6 College of Pharmacy, Gachon University, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea

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BMC Cancer 2014, 14:31  doi:10.1186/1471-2407-14-31

Published: 20 January 2014



Recent studies have shown that glucosamine inhibits the proliferation of various human cancer cell lines and downregulates the activity of COX-2, HIF-1α, p70S6K, and transglutaminase 2. Because the IGF-1R/Akt pathway is a common upstream regulator of p70S6K, HIF-1α, and COX-2, we hypothesized that glucosamine inhibits cancer cell proliferation through this pathway.


We used various in vitro assays including flow cytometry assays, small interfering RNA (siRNA) transfection, western blot analysis, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, reverse transcription-polymerase chain reaction, and in vivo xenograft mouse model to confirm anticancer activities of glucosamine and to investigate the molecular mechanism.


We found that glucosamine inhibited the growth of human non-small cell lung cancer (NSCLC) cells and negatively regulated the expression of IGF-1R and phosphorylation of Akt. Glucosamine decreased the stability of IGF-1R and induced its proteasomal degradation by increasing the levels of abnormal glycosylation on IGF-1R. Moreover, picropodophyllin, a selective inhibitor of IGF-1R, and the IGF-1R blocking antibody IMC-A12 induced significant cell growth inhibition in glucosamine-sensitive, but not glucosamine-resistant cell lines. Using in vivo xenograft model, we confirmed that glucosamine prohibits primary tumor growth through reducing IGF-1R signalling and increasing ER-stress.


Taken together, our results suggest that targeting the IGF-1R/Akt pathway with glucosamine may be an effective therapeutic strategy for treating some type of cancer.

Glucosamine; Anticancer agent; IGF-1R; Akt; Glycosylation; ER-stress