Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α

Jung, Chang-Wook; Jo, Jeong-Rang; Lee, Sang‐Han; Park, Yu-Kyoung; Jung, Nak-Kyun; Song, Dae‐Kyu; Bae, Jae‐Hoon; Nam, Ki-Young; Ha, Ji Soo; Park, In-Sook; Park, Gy-Young; Jang, Byeong‐Churl; Park, Jong‐Wook

doi:10.1016/j.tiv.2011.10.005

Cited by 26 publications

(12 citation statements)

References 48 publications

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“…Jung et al also reported that HIF‐1α was downregulated by glucosamine treatment in human oral cancer cells. Park et al reported similar results in prostate cancer cells . Therefore, HIF‐1 α suppression is a plausible GlcN antiallergic mechanism.…”

Section: Discussionmentioning

confidence: 68%

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

Jung

Kim

2017

Int Forum Allergy Rhinol

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Section: Discussionmentioning

confidence: 68%

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

Jung

Kim

2017

Int Forum Allergy Rhinol

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“…Although the specific cause(s) of death of individual mice have not been determined in the current study, it will be interesting to see whether and how GlcN affects not only glucose metabolism, but also cancer growth in chronically supplemented mice, as a number of studies insinuate that GlcN effectively reduces cancer cell proliferation434445464748.…”

Section: Discussionmentioning

confidence: 99%

D-Glucosamine supplementation extends life span of nematodes and of ageing mice

Priebs²,

et al. 2014

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D-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independent of the hexosamine pathway, extends Caenorhabditis elegans life span by impairing glucose metabolism that activates AMP-activated protein kinase (AMPK/AAK-2) and increases mitochondrial biogenesis. Consistent with the concept of mitohormesis, GlcN promotes increased formation of mitochondrial reactive oxygen species (ROS) culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation or impairment of aat-1-expression abolishes GlcN-mediated life span extension in an NRF2/SKN-1-dependent fashion. Unlike other calorie restriction mimetics, such as 2-deoxyglucose, GlcN extends life span of ageing C57BL/6 mice, which show an induction of mitochondrial biogenesis, lowered blood glucose levels, enhanced expression of several murine amino-acid transporters, as well as increased amino-acid catabolism. Taken together, we provide evidence that GlcN extends life span in evolutionary distinct species by mimicking a low-carbohydrate diet.

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“…Previously, studies have shown that HIF-1α expression is linked to tumor promotion in human OSCC (44) and correlates with the growth and adhesion in human OSCC cells (45). We and others have also recently demonstrated that HIF-1α protein is highly expressed in YD-8 tongue cancer cells (12) and DU145 prostate cancer cells (13), and long-term (24, 48 or 72 h) GS-HCl treatment inhibits proliferation, decreases survival and/or induces apoptosis in YD-8, DU145 and MDA-MB231 breast cancer cells (9,12,13). In view of this, the present study may have importance to address that i) downregulation of HIF-1α protein induced by short-term GS-HCl treatment may facilitate anti-proliferative, antisurvival and pro-apoptotic effects on YD-8 cells triggered by long-term GS-HCl treatment and ii) short-term treatment with GS-HCl alone and/or in combination with other anticancer therapeutics may be useful against OSCC and other malignances in which aberrant expression of HIF-1α protein plays an oncogenic role and/or confers drug resistance.…”

Section: Discussionmentioning

confidence: 56%

“…Moreover, it is suggested that the mechanisms underlying GS-mediated anti-proliferative and pro-apoptotic effect on cancer cells may include translocation of cathepsin D and downregulation of B-cell lymphoma-extra large (8), inhibition of p70S6 kinase (p70S6K) (9) and signal transducer and activator of transcription-3 (STAT-3) (10), induction of autophagy via the stimulation of endoplasmic reticulum (ER) stress (11), and activation of caspases via the intrinsic pathway (12). In recent studies, we and other investigators have also demonstrated the ability of GS to inhibit expression of HIF-1α, a tumor angiogenic transcription factor in YD-8 tongue cancer cells (12) and in DU145 prostate cancer cells (13), which may support its antitumor property.…”

Section: Introductionmentioning

confidence: 99%

Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells

Park

Jang

2014

International Journal of Oncology

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Abstract. Hypoxia-inducible factor-1 (HIF-1) is a tumor angiogenic transcription factor composed of an α and β subunit. We investigated the effect of glucosamine hydrochloride (GS-HCl) on the expression of HIF-1α and HIF-1β in serum-treated YD-8 human tongue cancer cells. While long-term (24 h) treatment with GS-HCl strongly repressed the expression of HIF-1α and HIF-1β at both the protein and mRNA levels, short-term (4 h) GS-HCl treatment inhibited HIF-1α at the protein level. Short-term GS-HCl treatment also decreased phosphorylation of p70S6K and S6, translation-related proteins. However, the results of subsequent pharmacological inhibition and protein stability analyses indicated that HIF-1α protein downregulation induced by short-term GS-HCl treatment was not through modulation of the mTOR/p70S6K/S6 signaling pathways, the 26S proteasomal and lysosomal activities and HIF-1α protein stability. Importantly, our further analyses identified that HIF-1α protein downregulation induced by short-term GS-HCl treatment was blunted by exogenous administration of the citric acid cycle metabolites citrate and 2-oxoglutarate, but not the glycolytic end byproducts pyruvate and lactate. These findings demonstrate firstly that short-term GS treatment selectively downregulates HIF-1α at the protein level in YD-8 cells via interference of production of the citric acid cycle metabolites. It is proposed that short-term GS-HCl exposure may be applied for the treatment of oral tumors with high expression of HIF-1α.

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Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α

Cited by 26 publications

References 48 publications

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

D-Glucosamine supplementation extends life span of nematodes and of ageing mice

Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells

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