Glucosamine, a naturally occurring amino monosaccharide, inhibits A549 and H446 cell proliferation by blocking G1/S transition

Ju, Yan; Yu, Alice L.; Sun, Xiuhua; Wu, Dongcheng; Zhang, Hongkai

doi:10.3892/mmr.2013.1584

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…Previous studies have reported that glucosamine inhibits cell growth [15,16] and cell-cycle progression [8,9,19] and induces apoptosis [20] in various cell lines. We therefore investigated whether the anti-cancer effect of glucosamine was associated with cell growth, cell-cycle arrest and apoptosis in NSCLC cell lines.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2014

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BackgroundRecent 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.MethodsWe 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.ResultsWe 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.ConclusionsTaken 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.

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Section: Resultsmentioning

confidence: 99%

“…Results of a recent study indicated that glucosamine induces G1 cell-cycle arrest in mesangial cells and human cancer cells through a mechanism involving decreased expression of cyclin D1 and increased expression of p21 Waf1/Cip1 , which are positive and negative regulators of cell cycle progression, respectively [8,9]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…On the other hand, some drugs that have cytotoxic effects on NSCLC also have obvious effects on SCLC, such as wentilactone A, which is cytotoxic to both H460 and H446 [16] , and glucosamine, which is cytotoxic to A549 and H446 cells [17] . Therefore, although there has been no report of the effect of EVO on SCLC to date, EVO may be a potential new drug candidate for the treatment of SCLC.…”

Section: Introductionmentioning

confidence: 99%

Evodiamine Induces G2/M Arrest and Apoptosis via Mitochondrial and Endoplasmic Reticulum Pathways in H446 and H1688 Human Small-Cell Lung Cancer Cells

Fang

Zhang

et al. 2014

PLoS ONE

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The goal of this study was to evaluate the ability of EVO to decrease cell viability and promote cell cycle arrest and apoptosis in small cell lung cancer (SCLC) cells. Lung cancer has the highest incidence and mortality rates among all cancers. Chemotherapy is the primary treatment for SCLC; however, the drugs that are currently used for SCLC are less effective than those used for non-small cell lung cancer (NSCLC). Therefore, it is necessary to develop new drugs to treat SCLC. In this study, the effects of evodiamine (EVO) on cell growth, cell cycle arrest and apoptosis were investigated in the human SCLC cell lines NCI-H446 and NCI-H1688. The results represent the first report that EVO can significantly inhibit the viability of both H446 and H1688 cells in dose- and time-dependent manners. EVO induced cell cycle arrest at G2/M phase, induced apoptosis by up-regulating the expression of caspase-12 and cytochrome C protein, and induced the expression of Bax mRNA and by down-regulating of the expression of Bcl-2 mRNA in both H446 and H1688 cells. However, there was no effect on the protein expression of caspase-8. Taken together, the inhibitory effects of EVO on the growth of H446 and H1688 cells might be attributable to G2/M arrest and subsequent apoptosis, through mitochondria-dependent and endoplasmic reticulum stress-induced pathways (intrinsic caspase-dependent pathways) but not through the death receptor-induced pathway (extrinsic caspase-dependent pathway). Our findings suggest that EVO is a promising novel and potent antitumor drug candidate for SCLC. Furthermore, the cell cycle, the mitochondria and the ER stress pathways are rational targets for the future development of an EVO delivery system to treat SCLC.

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“…Cyclin E binds and activates the cell cycle-dependent protein kinase cyclin-dependent kinase 2 (CDK2) to promote transition of the cell cycle from G 1 to S phase ( 72 ). Increased expression of CDK2 can cause chromosomal instability and accelerate the occurrence of cancer ( 73 ).…”

Section: Substrates and Mechanisms Of Fbxw7 Involved In Tumor Suppresmentioning

confidence: 99%

Function and regulation of F‑box/WD repeat‑containing protein 7 (Review)

Zhang

et al. 2020

Oncol Lett

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The ubiquitin-proteasome system is an important post-translational modification system involved in numerous biological processes, such as cell cycle regulation, gene transcription, signal transduction, apoptosis, differentiation and development. F-box/WD repeat-containing protein 7 (FBXW7) is one of the most studied F-box (FBX) proteins, serving as substrate recognition component of S phase kinase-associated protein 1-Cullin 1-FBX protein complexes. As a tumor suppressor, FBXW7 recognizes numerous proto-oncoproteins and promotes their ubiquitination and subsequent proteasomal degradation. FBXW7 is regulated at different levels, leading to tunable and specific control of the activity and abundance of its substrates. Therefore, genetic mutations or decreases in its expression serve an important biological role in tumor development. In-depth studies and identification of additional substrates targeted by FBXW7 have suggested a signaling network regulated by FBXW7, including its tumor-inhibitory role. The present review focused on the role of FBXW7 in tumor suppression and its application in cancer therapy. Contents 1. Introduction 2. Transcriptional and translational regulation of FBXW7 expression 3. Post-translational modifications of FBXW7 4. Genetic alterations of FBXW7 in cancers 5. Substrates and mechanisms of FBXW7 involved in tumor suppression 6. Therapeutic exploitation of FBXW7 signaling 7. Conclusions

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Glucosamine, a naturally occurring amino monosaccharide, inhibits A549 and H446 cell proliferation by blocking G1/S transition

Cited by 12 publications

References 26 publications

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

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

Evodiamine Induces G2/M Arrest and Apoptosis via Mitochondrial and Endoplasmic Reticulum Pathways in H446 and H1688 Human Small-Cell Lung Cancer Cells

Function and regulation of F‑box/WD repeat‑containing protein 7 (Review)

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