Apigenin Down-Regulates the Hypoxia Response Genes: HIF-1α, GLUT-1, and VEGF in Human Pancreatic Cancer Cells

Melstrom, Laleh G.; Salabat, Mohammad R.; Ding, Xian; Strouch, Matthew J.; Grippo, Paul J.; Mirzoeva, Salida; Pelling, Jill C.; Bentrem, David J.

doi:10.1016/j.jss.2010.10.041

Cited by 88 publications

(54 citation statements)

References 41 publications

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“…Expression of Glut-1 in endometrial lesions has also been demonstrated to be associated with cancer differentiation, and it is possible to use Glut-1 expression to effectively distinguish the malignant tendency from a benign tissue to atypical hyperplasia of the endometrium (29). Similarly, in pancreatic ductal adenocarcinoma and laryngeal cancer, Glut-1 expression levels have been demonstrated to be positively correlated with the clinical malignant stage (30). However, the associations between Glut-1 expression and clinicopathological parameters of osteosarcoma have not previously been reported.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of glucose transporter protein-1 overexpression in human osteosarcoma

et al. 2017

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Abstract. Although previous studies have demonstrated thatGlut-1 is the predominant glucose transporter, is significantly overexpressed in various types of tumor and is correlated with poor prognosis, the potential function and clinical value of Glut-1 expression in osteosarcoma remains largely unclear. In particular, the prospective associations between Glut-1 expression levels and clinicopathological factors remains to be elucidated. In the present study, immunohistochemistry was performed to detect Glut-1 protein expression in 51 paired osteosarcoma specimens and adjacent non-cancerous tissues, and reverse transcription-quantitative polymerase chain reaction analysis was performed to examine Glut-1 mRNA expression levels in 6 pairs of these tissues. Statistical analyses were conducted to determine the associations between Glut-1 expression and various clinicopathological parameters. Glut-1 protein was revealed to be overexpressed in 38 (74.5%) osteosarcoma tissues, but only in 6 (11.8%) adjacent non-cancerous tissues. Glut-1 mRNA levels were also upregulated in osteosarcoma tissues compared with adjacent non-cancerous tissues. While there were no clear statistical relationships between Glut-1 expression and patient sex, resection, tumor location, size, T stage and adjuvant treatment, Glut-1 expression levels were significantly associated with age, tumor-node-metastasis stage, lymph node metastasis and survival. The median survival time in patients with low Glut-1 expression levels was longer than in patients with a high expression level. Glut-1 was significantly overexpressed in osteosarcoma tissues, and Glut-1 expression was associated with clinicopathological factors which upregulate the invasion and metastasis of osteosarcoma, and may be a potential predictor of survival in patients with osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of glucose transporter protein-1 overexpression in human osteosarcoma

et al. 2017

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“…Two possible . Secondly, GLUT-1 activity is widely upregulated via hypoxia-inducible factor-1 in hypoxic conditions (24,25). Certain factors affect FDG uptake, including hypoxia, cell density and expression of glycolysis-associated proteins (26,27).…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Lǚ

Yang

et al. 2016

Oncology Letters

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Abstract.Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18 F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUV max ) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUV max value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer.

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“…The present results show that CME treatment could inhibit the myocardial HIF-1a protein expression and increase the myocardial PPARa protein expression. Several literature data show that among the CME polyphenols, chlorogenic acid, luteolin and apigenin can reduce hypoxia-induced angiogenesis by downregulating HIF-1a (Melstrom et al 2011;Fernando et al 2015;Park et al 2015). Our previous studies also exhibited that the polyphenol-rich CME may increase the hepatic PPARa expression (Cui et al 2014).…”

Section: Discussionmentioning

confidence: 77%

Chrysanthemum morifolium extract improves hypertension-induced cardiac hypertrophy in rats by reduction of blood pressure and inhibition of myocardial hypoxia inducible factor-1alpha expression

Gao

Zhu

Zhou

et al. 2016

Pharmaceutical Biology

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(2016) Chrysanthemum morifolium extract improves hypertension-induced cardiac hypertrophy in rats by reduction of blood pressure and inhibition of myocardial hypoxia inducible factor-1alpha expression, Pharmaceutical Biology, 54:12, 2895-2900, DOI: 10.1080/13880209.2016 Context: Chrysanthemum morifolium Ramat. (Asteraceae) extract (CME) possesses a vasodilator effect in vitro. However, the use of polyphenol-rich CME in the treatment of hypertension-induced cardiac hypertrophy has not been reported. Objective: We investigated the effect of polyphenol-rich CME on hypertension-induced cardiac hypertrophy in rats and its possible mechanism of action. Materials and methods: The Sprague-Dawley rat model with cardiac hypertrophy was induced by renovascular hypertension. The blood pressure, cardiac weight index, free fatty acids (FFA) in serum and myocardium, and protein expressions of myocardial hypoxia inducible factor-1a (HIF-1a), peroxisome proliferator-activated receptor a (PPARa), carnitine palmitoyltransferase-1a (CPT-1a), pyruvate dehydrogenase kinase-4 (PDK-4) and glucose transporter-4 (GLUT-4) were measured after treating hypertensive rats with polyphenol-rich CME of anthodia 75-150 mg/kg once daily for 4 weeks. A myocardial histological examination was also conducted. Results: After CME treatment, the blood pressure, cardiac weight and cardiac weight index decreased by 5.7-9.6%, 9.2-18.4% and 10.9-20.1%, respectively, and the cardiomyocyte cross-sectional area also decreased by 8.3-30.4%. The CME treatment simultaneously decreased the FFA in serum and myocardium and protein expressions of myocardial HIF-1a and GLUT-4, and increased the protein expressions of myocardial PPARa, CPT-1a and PDK-4, especially in the CME 150 mg/kg group (p < 0.05 or p < 0.01). Discussion and conclusion: Polyphenol-rich CME may alleviate hypertensive cardiac hypertrophy in rats. Its mechanisms may be related to the reduction of blood pressure and amelioration of the myocardial energy metabolism. The latter may be attributed to the inhibition of HIF-1a expression and subsequent modulation of PPARa-mediated CPT-1a, PDK-4 and GLUT-4 expressions. ARTICLE HISTORY

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Apigenin Down-Regulates the Hypoxia Response Genes: HIF-1α, GLUT-1, and VEGF in Human Pancreatic Cancer Cells

Cited by 88 publications

References 41 publications

Clinicopathological significance of glucose transporter protein-1 overexpression in human osteosarcoma

Clinicopathological significance of glucose transporter protein-1 overexpression in human osteosarcoma

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Chrysanthemum morifolium extract improves hypertension-induced cardiac hypertrophy in rats by reduction of blood pressure and inhibition of myocardial hypoxia inducible factor-1alpha expression

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