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

BMC Cancer

Ki-Hoon Song¹  Ju-Hee Kang⁴  Jong-Kyu Woo³  Jeong-Seok Nam⁶  Hye-Young Min⁵  Ho-Young Lee⁵  Soo-Youl Kim¹  Seung-Hyun Oh² 

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

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

[3] Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 406-840, Republic of Korea

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

[5] College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea

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

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

Others  :  859125
DOI  :  10.1186/1471-2407-14-31

 received in 2013-09-03, accepted in 2014-01-15,  发布年份 2014

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Song et al.; licensee BioMed Central Ltd.

【 图 表 】

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