Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Zhang, J.; Js, Zhu; Zhou, Zun-Qiang; Wx, Chen; Chen, N-W.

doi:10.1177/1721727x1201000103

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…HMGB1 interferes with the apoptotic machinery at the level ofcaspase-9 activation and inhibits cell apoptosis via c-IAP2 induction in the pathogenesis of colon carcinoma (28), while RAGE limits apoptosis through a p53dependent mitochondrial pathway in tumor cell (29). Previous studies have shown that blockade of HMGBl-RAGE axis by EP inhibits the growth and metastasis of malignant tumors via negative regulation ofPCNA, MMP-9 and positive regulation of p53 (24,30). Our present study showed that EP suppressed GBC growth and invasion via negative regulation ofPCNA, MMP-9 and positive regulation ofp53, which might be mediated byHMGBl-RAGE axis.…”

Section: Discussionmentioning

confidence: 99%

“…But, targeting HMGBI by EP inhibits hepatic tumor growth (22) and exerts antitumor activity via inhibition of indoleamine 2, 3-dioxygenaseour (23). In addition, based on our previous research, EPmediated inhibition of HMGBI-RAGE axis could suppress growth and invasion of gastric cancer cells and severe combined immunodeficiency mouse orthotopic implantation model (24). Thus, EP may have the potential as a new multi-functional drug candidate for cancer therapy and be widely used in clinical settings to treat malignant tumMoreover, in the present study, the possible molecular mechanism of EP on GBC cell growth and invasion need be comprehensively explored.…”

Section: Fig 4 Effects Ofep Administration On Gbc Cell Invasion A)mentioning

confidence: 99%

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Ethyl Pyruvate Administration Suppresses Growth and Invasion of Gallbladder Cancer Cells via Downregulation of Hmgb1-Rage Axis

et al. 2012

Int J Immunopathol Pharmacol

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The first two authors contributed equally to this work High mobility group box Bl (HMGBl)-receptor for advanced glycation endproducts (RAGE) axis has been previously known to be involved in carcinogenesis and development of multiple malignancies. Some studies have confirmed that Ethyl pyruvate (EP), a potent inhibitor of HMGBl, exerts the therapeutic effects on metastatic live tumor from gastric cancer. However, the effects and possible molecular mechanisms of EP on gallbladder cancer (GBC) need to be further explored. In the present study, human GBC cell lines (GBC-SD and SGC-996) were treated with different concentrations of EP. Then, the expression levels of HMGBl, RAGE and some transcription factors were identified by Real-time PCR and Western blot assays. Cell proliferative activities indicated by MTT assay, invasive potential by Transwell assay and cell apoptosis and cycle distribution were performed for functional analysis of GBC cell lines in vitro. As a result, EP decreased the expression of HMGBll, RAGE, PCNA and matrix metallopeptidase-9 (MMP-9), while it increased the expression of p53. Moreover, EP administration decreased GBC cell proliferation, inhibited the invasive potential, and induced apoptosis and cycle arrest in S phase in GBC cells. In conclusion, EP administration inhibits growth and invasion of gallbladder cancer cells possibly via down-regulation of the HMGBl-RAGE axis, suggesting that EP may playa critical role in the treatment of cancer in conjunction with other therapeutic agents.High mobility group BI (HMGBI) has been known for its intracellular function as the intranuclear non-histone DNA binding protein and is regarded as an essential position in DNA repair. HMGBI and its counter-receptor, receptor for advanced glycation endproducts (RAGE), represent suitable targets for investigation, integrating many aspects of modem biology, particularly that associated with cancer (1). Originally, amphoterin, the major production of HMGB1, is over-expressed and closely associated with tumor invasion and metastasis. In human dendritic cells, RAGE is required for the effect of HMGB1 on cell expansion and survival. HMGB1/ RAGE interaction results in downstream activation of MAPK and NF-KB, representing a profitable evolutionary mechanism (2). Over-expression of HMGBI/RAGE, especially with membranous pattern, is associated with malignant potential

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Section: Discussionmentioning

confidence: 99%

Section: Fig 4 Effects Ofep Administration On Gbc Cell Invasion A)mentioning

confidence: 99%

Ethyl Pyruvate Administration Suppresses Growth and Invasion of Gallbladder Cancer Cells via Downregulation of Hmgb1-Rage Axis

et al. 2012

Int J Immunopathol Pharmacol

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“…Exercise has been shown to enhance in vitro macrophage antitumor cytotoxicity (60)(61)(62)(63)(64) and, in accordance with the immune surveillance theory, it is to be expected that moderate exercise protects against malignancy whereas exhaustive exercise is linked to increased cancer risk. Relatively low intake of fruit and vegetables is a risk factor for many of the most important chronic diseases (65)(66)(67)(68)(69)(70), whereas greater consumption of natural products -including, spices, nuts, whole-grain cereals, legumes, fruits and vegetables is associated with a lower risk of many diseases (71)(72)(73)(74)(75)(76). Chronic inflammation is one of the foremost risk factors for different types of cancer.…”

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confidence: 99%

Nutrition and Cancer Prevention

Tetè

Nicoletti

Saggini

et al. 2012

Int J Immunopathol Pharmacol

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Cancer cells invade surrounding tissues and metastasize to distant sites. Diet high in fat is a strong link to, and perhaps causes, a high incidence of tumours. Trans-fatty acid might impair the function and it could be involved in the development of cancer. Cholesterol is also strongly suspected to be involved in the development of tumours, therefore it is important for everyone to eat well, especially for people with cancer to prevent the body tissues from breaking down and helping to rebuild the normal tissue that may have been affected by the treatments. Factors secreted by adipocytes and macrophages such as TNF-alpha and other inflammatory proteins are involved in inflammation in cancer. In addition, MCSF which up-regulates adipocyte tissue is also important for the stimulation of fat cell proliferation and is expressed by human adipocytes. Many cytokines, such as IL-1, IL-6, IL-8, IL-32, IL-33 and MCP-1, are biomarkers for cancer and chronic diseases along with transcription factors NFκB and AP-1; these last two factors are important bioactive substances on the molecular mechanism of the control of genes which in turn affect cellular metabolism. In this paper we revisit the interrelationship between cancer and metabolism.

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“…It has been reported that mast cells express leptin and leptin receptors, a finding implicating paracrine or autocrine immunomodulatory effects of leptin on mast cells (32)(33)(34)(35). Leptin may playa role in ASD.…”

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confidence: 99%

Impact of Immunity in Autism Spectrum Disorders

et al. 2013

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Autism spectrum disorders (ASDs) are childhood psychopathologies characterized by having difficulties in social interaction, verbal and non-verbal communication as well as sensor motor movements. Evidence suggests that in ASDs environmental toxicant exposure, genetic and mitochondrial dysfunction are involved associated with abnormal immune response with allergic problems and elevated serum IgE. ASDs present the major cytokine and chemokine dysfunction in CNS and is mediated by an increase of pro-inflammatory cytokine levels in the brain, such as TNF, IL-1, IFN-γ, IL-6, IL-8 and others. Mast cells, which are also implicated in ASDs, are worsened by stress and produce proinflammatory cytokines and can be stimulated by neurotensin in the brain and gut, contributing also to the inflammatory response. However, the exact etiology of ASDs remains largely unknown.

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Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Cited by 5 publications

References 29 publications

Ethyl Pyruvate Administration Suppresses Growth and Invasion of Gallbladder Cancer Cells via Downregulation of Hmgb1-Rage Axis

Ethyl Pyruvate Administration Suppresses Growth and Invasion of Gallbladder Cancer Cells via Downregulation of Hmgb1-Rage Axis

Nutrition and Cancer Prevention

Impact of Immunity in Autism Spectrum Disorders

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