Increased expression of nuclear factor-?B/RelA is correlated with tumor angiogenesis in human colorectal cancer

Yu, Honggang; Zhong, Xia; Yang, Yanning; Luo, Haitao; Yu, Jie-Ping; Meier, Juris J.; Schrader, Henning; Bastian, Andreas; Schmidt, Wolfgang E.; Schmitz, Frank

doi:10.1007/s00384-003-0494-z

Cited by 47 publications

(46 citation statements)

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“…Once activated, NF-kB promotes cell survival through expression of genes coding for antiapoptotic proteins (c-IAP1, c-IAP2, bfl-1, and Bcl-xl) and supports resistance of tumour cell to treatments by inducing the expression of the multidrug resistance proteins (Pahl, 1999). Furthermore, NF-kB could largely participate to the tumorigenic process through expression of genes coding for growth factors and cell cycle regulators (Van Antwerp et al, 1996;Wang et al, 1996) as well as it could promote metastasis through induction of extracellular matrix-degrading enzymes and angiogenesis through vascular endothelial growth factor expression (Yu et al, 2004). The inhibition of NF-kB could therefore affect tumour cells at different steps of their pathological process.…”

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confidence: 99%

Pharmacological targeting of NF-κB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells

et al. 2008

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NF-kB interferes with the effect of most anti-cancer drugs through induction of anti-apoptotic genes. Targeting NF-kB is therefore expected to potentiate conventional treatments in adjuvant strategies. Here we used a pharmacological inhibitor of the IKK2 kinase (AS602868) to block NF-kB activation. In human colon cancer cells, inhibition of NF-kB using 10 mM AS602868 induced a 30 -50% growth inhibitory effect and strongly enhanced the action of SN-38, the topoisomerase I inhibitor and CPT-11 active metabolite. AS602868 also potentiated the cytotoxic effect of two other antineoplasic drugs: 5-fluorouracil and etoposide. In xenografts experiments, inhibition of NF-kB potentiated the antitumoural effect of CPT-11 in a dose-dependent manner. Eighty-five and 75% decreases in tumour size were observed when mice were treated with, respectively, 20 or 5 mg kg À1 AS602868 associated with 30 mg kg À1 CPT-11 compared to 47% with CPT-11 alone. Ex vivo tumour analyses as well as in vitro studies showed that AS602868 impaired CPT-11-induced NF-kB activation, and enhanced tumour cell cycle arrest and apoptosis. AS602868 also enhanced the apoptotic potential of TNFa on HT-29 cells. This study is the first demonstration that a pharmacological inhibitor of the IKK2 kinase can potentiate the therapeutic efficiency of antineoplasic drugs on solid tumours.

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confidence: 99%

Pharmacological targeting of NF-κB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells

et al. 2008

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“…The most likely reason that a combination of cytostatic and alpha lipoic acid exerts an inhibitory effect on the NF-κB levels would be strong antioxidant properties of the alpha lipoic acid, which thereby reduce the inducible effect. But the fact that the ALA applied solely and thus was not being able to completely suppress the synthesis and the activation of the NF-κB, acknowledges that cancer cells produce a constitutive NF-κB not only in response to the epigenetic factors (oxidative stress), but most likely as a mode for their survival (25,26,27). This is why it is inexplicable that the combined use of lipoic acid and 5-FU has resulted in increased effect of the cytostatic applied.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines

Damnjanović¹,

Kocić²,

Najman³

et al. 2014

BLL

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Abstract:Objectives: The nuclear factor κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer. The aim of this study was to examine the infl uence of the alpha lipoic acid in the chemoprevention of colon and cervix carcinoma in vitro. Background: In recent years, special attention has been paid to the potential chemopreventive properties of antioxidants. There are no published data on the impact of alpha lipoc acid of chemoprevention of cervix and colon cancer. Methods: We examined the effect of alpha lipoic acid alone or in combination with cisplatin and 5-fl uorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The measurement of the level of transcription factor NF-κB was also performed in the cells of both cell lines. Results: At least one of the mechanisms of the antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa cells at high concentrations, the transcription factor NF-κB, may be involved, as well as the products of transcription of genes that are under its control. Conclusion: The alpha lipoic acid has proven to be a promising candidate in the combat arena against cancer (Tab. 4, Ref. 31). Text in PDF www.elis.sk.

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“…It is known that the process of angiogenesis plays a central role in local tumor growth and in the development of distant metastases by facilitating the entry of cells into the circulation 1 . Immunohistochemical studies have demonstrated that the intensive formation of tumoral microvessels stimulated by angiogenic factors contributes towards tumor angiogenesis in colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Assessment of angiogenesis expression and its relationship with prognosis of colorectal cancer by conventional and computer-assisted histopathological image analysis

et al. 2006

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Assessment of angiogenesis expression and its relationship with prognosis of colorectal cancer by conventional and computer-assisted histopathological image analysis 1Investigação da expressão da angiogênese e sua relação com o prognóstico do câncer colorretal pela análise convencional e informatizada da imagem histopatológica ABSTRACT Purpose:To quantify the degree of angiogenesis by conventional method (microvessel density, MVD) and computerized method (endothelial area, EA), and to evaluate their relationships with the prognosis of patients operated on for colorectal adenocarcinoma. Methods: Tumoral angiogenesis was studied by means of an immunohistochemical technique, using CD 34, on 126 patients; to quantify the angiogenesis, MVD (defined as number of microvessels per mm 2 ) and EA measurement (defined as the area occupied by EA in the microscope field). A computerized method, IMAGELab software was utilized to quantify endothelial area. Results: The mean number of microvessels was 128.6 MV/mm 2 (SD = 44.5) and the mean EA was 4.3% (SD = 2.1). The Pearson method demonstrated a low correlation coefficient between MVD and EA (r = 0.429). No relationship between MVD and EA was observed with regard to relapse-free interval and overall survival. Conclusion:The histological analysis of angiogenesis expression in patients with colorectal adenocarcinoma can be performed either by computer-assisted image analysis of endothelial area or by conventional microvessels counting. Both methods did not show any significant relationship between these angiogenesis parameters with relapse-free interval and overall survival. Key words: Colonic Neoplasms. Image Processing. Computer-Assisted. Prognosis. RESUMOObjetivo: Quantificar a intensidade da angiogênese pelo método convencional (densidade microvasal, DMV) e pelo método informatizado, área endothelial (AE) e avaliar a sua correlação com o prognóstico de doentes operados por adenocarcinoma colorretal. Métodos: A angiogênese tumoral foi investigada por meio de técnica imuno-histoquímica, utilizando-se CD-34, em 126 doentes; para quantificar a angiogênese, a microdensidade vascular, definida como o número de microvasos por mm 2 e a medida da área endotelial, definida como a área ocupada pelo endotélio vascular identificada no campo microscópico foram empregadas. Um programa computadorizado, o IMAGELab foi empregado para a quantificação da área endothelial. Resultados: A media do número de microvasos foi de 128,6 MV/mm 2 (d esvio padrão de 44,5). O método do coeficiente de Pearson demonstrou uma baixa correlação entre a DMV e a AE (r=0,429). Nenhuma correlação entre a DMV e AE com o intervalo livre de doença e tempo global de sobrevida foi observada. Conclusão: A análise histológica da expressão angiogênica em doentes com adenocarcinoma colorretal pode ser realizada tanto da forma informatizada, na quantificação da área endotelial, como pela convencional, na contagem dos microvasos. Ambos métodos não demonstraram relação estatisticamente significante entre estes parâmetros de an...

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Increased expression of nuclear factor-?B/RelA is correlated with tumor angiogenesis in human colorectal cancer

Abstract: Our results suggest that increased expression of NF-kappa B/RelA contributes to tumor angiogenesis in colorectal cancer. VEGF may play an important role in mediating the NF-kappa B/RelA angiogenic pathway.

Cited by 47 publications

References 14 publications

Pharmacological targeting of NF-κB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells

Pharmacological targeting of NF-κB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells

Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines

Assessment of angiogenesis expression and its relationship with prognosis of colorectal cancer by conventional and computer-assisted histopathological image analysis

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