Cancer Cell Int. 2009 Sep 10;9:25.
Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells through inhibition of STAT3 signaling.
Chesnokov V,
Sun C,
Itakura K.
Department of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte road, Duarte, California 91010, USA.
vchesnokov@coh.org
BACKGROUND:
Glucosamine is known as a toxic agent for several malignant cell lines and transplanted tumors with little toxicity to normal host tissues. However, the mechanisms underlying anticancer activity of glucosamine are poorly understood. To study the mechanisms, the
human prostate cancer DU145 cells were used for the model. RESULTS: Glucosamine at concentration 2 mM suppressed proliferation and induced death of DU145 cells. Detailed analysis showed that glucosamine decreased DNA synthesis, arrested cell cycle at G1 phase and induced apoptosis. The effects of glucosamine were associated with up-regulation of p21waf1/cip, a CDK inhibitor. Our further studies identified glucosamine as an inhibitor of signal transducer and activator of transcription (STAT) 3 which is constitutively activated in many cancer cells including DU145 cells. Glucosamine inhibited phosphorylation of STAT3 at the Tyr705 residue and as a result, reduced STAT3 DNA binding and transcriptional activities. Indeed, the expression of apoptosis inhibitor survivin, which is well known target of STAT3, was suppressed. Contrary to DU145 cells, glucosamine did not affect proliferation of other human prostate cancer PC-3 and C4-2B cells, in which STAT 3 signal pathway is not constitutively active. CONCLUSION:
Our data identifies glucosamine as a suppressor of STAT3 signaling and suggests that anticancer activity of glucosamine may be attributed to the suppression of STAT3 activity. Potential application of glucosamine for the treatment of tumors with constitutively active STAT3 is proposed.
PMID: 19744341 [PubMed]
J Cell Biochem. 2009 Oct 1;108(2):489-98.
Glucosamine inhibits IL-1beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation.
Tsai CY,
Lee TS,
Kou YR,
Wu YL.
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Inflammation is a complex process involving cytokine production to regulate host defense cascades. In contrast to the therapeutic significance of acute inflammation, a pathogenic impact of chronic inflammation on cancer development has been proposed. Upregulation of inflammatory cytokines, such as IL-1beta and IL-8, has been noted in prostate cancer patients and IL-8 has been shown to promote prostate cancer cell proliferation and migration; however, it is not clear whether IL-1beta regulates IL-8 expression in prostate cancer cells. Glucosamine is widely regarded as an anti-inflammatory agent and thus we hypothesized that if IL-1beta activated IL-8 production in prostate cancer cells, then glucosamine ought to blunt such an effect. Three prostate cancer cell lines, DU-145, PC-3, and LNCaP, were used to evaluate the effects of IL-1beta and glucosamine on IL-8 expression using ELISA and RT-PCR analyses. IL-1beta elevated IL-8 mRNA expression and subsequent IL-8 secretion. Glucosamine significantly inhibited IL-1beta-induced IL-8 secretion. IL-8 appeared to induce LNCaP cell proliferation by MTT assay; involvement of IL-8 in IL-1beta-dependent PC-3 cell migration was demonstrated by wound-healing and transwell migration assays. Inhibitors of MAPKs and NFkappaB were used to pinpoint MAPKs but not NFkappaB being involved in IL-1beta-mediated IL-8 production. IL-1beta-provoked phosphorylation of all MAPKs was notably suppressed by glucosamine. We suggest that IL-1beta can activate the MAPK pathways resulting in an induction of IL-8 production, which promotes prostate cancer cell proliferation and migration. In this context, glucosamine appears to inhibit IL-1beta-mediated activation of MAPKs and therefore reduces IL-8 production; this, in turn, attenuates cell proliferation/migration. (c) 2009 Wiley-Liss, Inc.
PMID: 19626664 [PubMed - indexed for MEDLINE]
Biochem Biophys Res Commun. 2009 Apr 24;382(1):96-101. Epub 2009 Feb 28.
D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells.
Park JY,
Park JW,
Suh SI,
Baek WK.
Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.
D-glucosamine has been reported to inhibit proliferation of cancer cells in culture and in vivo. In this study we report a novel response to D-glucosamine involving the translation regulation of hypoxia inducible factor (HIF)-1alpha expression. D-glucosamine caused a decreased expression of HIF-1alpha under normoxic and hypoxic conditions without affecting HIF-1alpha mRNA expression in DU145 prostate cancer cells. D-glucosamine inhibited HIF-1alpha accumulation induced by proteasome inhibitor MG132 and prolyl hydroxylase inhibitor DMOG suggesting D-glucosamine reduces HIF-1alpha protein expression through proteasome-independent pathway. Metabolic labeling assays indicated that D-glucosamine inhibits translation of HIF-1alpha protein. In addition, D-glucosamine inhibited HIF-1alpha expression induced by serum stimulation in parallel with inhibition of p70S6K suggesting D-glucosamine inhibits growth factor-induced HIF-1alpha expression, at least in part, through p70S6K inhibition. Taken together,
these results suggest that D-glucosamine inhibits HIF-1alpha expression through inhibiting protein translation and provide new insight into a potential mechanism of the anticancer properties of D-glucosamine.
PMID: 19254699 [PubMed - indexed for MEDLINE]
Suggesting why antibiotics and glucosamine have anticancer effects?
Curr Med Chem. 2009;16(29):3805-27.
Selective matrix metalloproteinase inhibitors for cancer.
Lia NG,
Shib ZH,
Tang YP,
Duan JA.
Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210046, Nanjing, Jiangsu, P.R. China.
The matrix metalloproteinases are a family of nearly 30 enzymes that are intimately involved in tissue remodeling. Disease processes associated with the matrix metalloproteinases are generally related to imbalance between the inhibition and activation of matrix metalloproteinases resulting in excessive degradation of the extracellullar matrix. These include osteoarthritis, rheumatoid arthritis, tumor metastasis and congestive heart failure. Despite massive research and development efforts,
there are only two drugs launched on the market: periostat (doxycycline), a tetracycline used for periodontal disease and glucosemine sulfate, for osteoarthritis. Possible reasons for the low success rate of matrix metalloproteinase inhibitors in the clinic are mainly from unwanted side effects caused by their
lack of selectivity, since inhibition of collagenase-1 may be responsible for the musculoskeletal side effects observed clinically with broad-spectrum inhibitors. Considering these data, many efforts were directed to developing a more selective second generation of inhibitors against the specific matrix metalloproteinases believed to be involved in the different pathologies. This review mainly focuses on selective matrix metalloproteinase inhibitors development on matrix metalloproteinases in terms of antitumor since the late 90s, in terms of synthetic compounds of low molecular mass incorporating specific zinc-binding groups, natural products and their derivatives. Through these methods, new hope is emerging in the form of synthetic and natural matrix metalloproteinase inhibitors for the prevention and treatment of cancer.
PMID: 19747139 [PubMed - indexed for MEDLINE]
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