Anti-lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO

作者：Yu, Zhanwu; Ju, Yinghua; Liu, Hongxu^*

来源：Molecular Medicine Reports, 2017, 16(3): 3395-3400.

DOI：10.3892/mmr.2017.6976

• glucosamine
• forkhead box O
• phosphoinositide 3-kinase/AKT
• mitogen-activated protein kinase/extracellular signal-regulated kinase
• O-GlcNAc modification

Lung cancer is the most common cause of cancer-associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti-lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)-FOXO1/3, AKT, p-AKT, extracellular signal-regulated kinase (ERK) and p-ERK, and the levels of beta-O-linked N-acetylglucosamine (O-GlcNAc)-modified FOXO1 protein. Immunoprecipitation was performed to purify O-GlcNAc-modified protein prior to immunoblotting. Glucosamine inhibited FOXO1- and FOXO3-specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti-lung cancer mechanism of glucosamine. The present study also examined the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK pathways, which induce FOXO1- and FOXO3-specific site phosphorylation. The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine-induced O-GlcNAc modification. These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O-GlcNAc modification-induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3.

• 出版日期2017-9
• 单位辽宁省肿瘤医院; 中国医科大学