d-Glucosamine down-regulates HIF-1α through inhibition of protein translation in DU145 prostate cancer cells

Park, Jee-Young; Park, Jong‐Wook; Suh, Seong-Il; Baek, Won-Ki

doi:10.1016/j.bbrc.2009.02.129

Cited by 21 publications

(19 citation statements)

References 19 publications

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“…Several antitumor agents including EF24 (curcumin analog), 13 glucosamine, 14 apigenin, 15 quercetin, 16 NS398 (Cox-2 inhibitor), 17 doxorubicin (anthracyclin), 18 trichostatin A (histone deacetylase inhibitor) 19 and rapamycin (mTOR inhibitor) 20 have been shown to inhibit HIF-1a in numerous cancer cell types including those of the prostate. These agents may lead to decreased HIF-1a DNA binding, decreased HIF-1a synthesis or decreased HIF-1a transactivation.…”

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confidence: 99%

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Sinha

Null

Wolter

et al. 2011

Intl Journal of Cancer

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Alternative strategies are needed to control growth of advanced and hormone refractory prostate cancer. In this regard, we investigated the efficacy of methylseleninic acid (MSeA), a penultimate precursor to the highly reactive selenium metabolite, methylselenol, to inhibit growth of invasive and hormone refractory rat (PAIII) and human (PC-3 and PC-3M) prostate cancer cells. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as well as reduces weights of tumors generated by PAIII cells treated ex vivo. A significant reduction in the number of metastatic lung foci by MSeA treatment was also noted in Lobund-Wistar rats. The PAIII cells along with PC-3, DU145 and PC-3M cells undergo apoptosis after MSeA treatments in both normoxia and hypoxia. Treatment of metastatic rat and human prostate cancer cell lines with MSeA decreased hypoxiainducible factor-1a (HIF-1a) levels in a dose-dependent manner. Additionally, HIF-1a transcription activity both in normoxic and hypoxic conditions is reduced after MSeA treatment of prostate cancer cells. Furthermore, VEGF and GLUT1, downstream targets of HIF-1a, were also reduced in prostate cancer cells after MSeA treatment. Our study illustrates the efficacy of MSeA in controlling growth of hormone refractory prostate cancer by downregulating HIF-1a, which is possibly occurring through stabilization or increase in prolyl hydroxylase activity.In men with advanced prostate cancer, hormone therapy is accepted as the initial treatment of choice and produces good responses in most patients. However, many patients relapse and become resistant to further hormone manipulation. Radical prostatectomy is recommended for treatment of localized prostate cancer. Unfortunately, local recurrences occur in up to one-third of patients by 5 years after surgery.1 Furthermore, a combination of hormone therapy with radical prostatectomy in patients with localized disease resulted in 5-year disease-free survival of 64%. 2Effective radiation therapy requires the presence of oxygen.3 As a result of rapid mitotic growth and clonal expansion, tumor cells are usually forced away from vessels beyond effective diffusion distance of oxygen and thrive remarkably well within a hypoxic environment. This tumor hypoxia may lead to resistance to radiation and chemotherapy.4 Hypoxia within solid tumors induces hypoxia-inducible factor (HIF)-1a, 5 and its elevation in prostate cancer cells may attribute to enhanced growth rates, survival and increased metastatic potential. 6HIF-1 is a heterodimer composed of an inducible a-subunit that confers the sensitivity to oxygen and a constitutively expressed b-subunit, aryl hydrocarbon receptor nuclear translocator.7 Under normoxic conditions after a post-translational hydroxylation by prolyl hydroxylase (PHD), HIF-1a interacts with tumor suppressor von-Hippel-Lindau protein and is rapidly degraded via ubiquitin-dependent proteasome pathway. 8 Hypoxia induces a rapid increase in HIF-1a protein stability and transcriptional activity, 9 resulting in the activat...

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confidence: 99%

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Sinha

Null

Wolter

et al. 2011

Intl Journal of Cancer

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“…For instance, it is shown that 24 h treatment with GS-HCl (5 mM) inhibits the activity of S6K in DU145 prostate cancer cells and MDA-MB-231 breast cancer cells and the inhibition is important for GS-HCl-induced anti-proliferative effects on these cancer cells (9). The same group also has addressed that 10 h treatment with GS-HCl (5 mM) inhibits S6K signaling pathway and importantly the inhibition is in part linked to inhibition of HIF-1α at protein level in serum-treated DU145 cells (13). In the present study, we have shown that short-term (2 or 4 h) treatment with GS-HCl (10 mM) largely blocks phosphorylation of not only S6K but also S6 in YD-8 cells (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…There are previous studies stating that GS inhibits protein, mRNA, DNA synthesis in mouse leukemic cells L5178Y, which may contribute to its antitumor effect (6,7). However, it has been shown that short-term (2 h) treatment with GS-HCl (2 or 5 mM) does not affect global protein synthesis in DU145 cells (13). In this study, we demonstrated that short-term (2 or 4 h) GS-HCl treatment increased phosphorylated forms of eIF-2α in YD-8 cells ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…However, there is increasing body of evidence suggesting the hypoxia-independent upregulation of HIF-1α expression. For instance, it is shown that a number of factors, including serum, interleukin-1β, insulin, manganese, and ginsenoside-Rg1, induces expression of HIF-1α through transcriptional and/or translational upregulation in many types of cells under normoxia (13,(20)(21)(22)(23). Evidence also strongly suggests that activities of many intracellular signaling proteins, such as phosphoinositide 3-kinase, extracellular-regulated protein kinase-1/2, c-jun N-terminal kinase-1, S6, p38 mitogen-activated protein kinase, epidermal growth factor receptor/p70S6K, protein kinase B/mammalian target of rapamycin-p70S6K, and mTOR/p70S6K/S6, are necessary for normoxic induction of HIF-1α expression in response to extracellular stimuli (22,(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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

Jung

Kim

2017

Int Forum Allergy Rhinol

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d-Glucosamine down-regulates HIF-1α through inhibition of protein translation in DU145 prostate cancer cells

Cited by 21 publications

References 19 publications

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

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

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

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