In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. LB-99-LB-99
Abstract:
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. Objective: 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: Cell viability was assayed by MTT assay. Total RNA was isolated and reverse transcribed to cDNA for real-time PCR quantification of genes. Western blotting as performed for analyzing expression of proteins. Flow cytometry was performed for apoptosis and cell progression. Balbc/nu mice used in the study for validating results in vivo. Results: We found that glucosamine inhibited the growth of human non-small cell lung cancer cells in vitro and in vivo and negatively regulated the expression of IGF-1R and phosphorylation of Akt. In other types of cancer cells, including head and neck, breast, prostate, and colon carcinoma cell lines, glucosamine-sensitive cell lines exhibited a more significant decrease in IGF-1R and pAkt levels than glucosamine-resistant cell lines. Interestingly, most of the glucosamine-resistant cell lines have “hot-spot” mutations in PIK3CA, the p110α subunit of PI3K, or loss of PTEN, a negative regulator of Akt activation. In contrast, most of the glucosamine-sensitive cell lines have normal PIK3CA and PTEN genes. Glucosamine decreased the pAkt level through activation of IGF-1R more efficiently in the glucosamine-sensitive than in the glucosamine-resistant cell lines. Furthermore, co-treatment of cells with glucosamine and LY294002, a specific inhibitor of PI3K, significantly enhanced the anticancer effect of glucosamine in the glucosamine-resistant cell lines, whereas transient inhibition of PTEN by siRNA partially decreased the glucosamine sensitivity in the resistant and sensitive cell lines. Conclusions: Our results indicate that glucosamine is an effective inhibitor of the IGF-1R/Akt pathway and that glucosamine sensitivity of each cell line was affected by the mutation status of PIK3CA and PTEN. Citation Format: Ju-Hee Kang, Ki-Hoon Song, Jeong-Seok Nam, Hye-Young Min, Ho-Young Lee, Sung-Dae Cho, Soo-Youl Kim, Seung Hyun Oh. The novel IGF-IR/Akt-dependent anticancer activities of glucosamine are affected by PIK3CA hot-spot mutations and PTEN deletion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-99. doi:10.1158/1538-7445.AM2013-LB-99
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-LB-99
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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