Antitumor effects of the novel NF-kappa B inhibitor dehydroxymethyl-epoxyquinomicin on human hepatic cancer cells: Analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production (Articolo in rivista)

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  • Antitumor effects of the novel NF-kappa B inhibitor dehydroxymethyl-epoxyquinomicin on human hepatic cancer cells: Analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production (Articolo in rivista) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Alternative label
  • Poma P, Notarbartolo M, Labbozzetta M, Sanguedolce R, Alaimo A, Carina V, Maurici A, Cusimano A, Cervello M, D'Alessandro N. (2006)
    Antitumor effects of the novel NF-kappa B inhibitor dehydroxymethyl-epoxyquinomicin on human hepatic cancer cells: Analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production
    in International journal of oncology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Poma P, Notarbartolo M, Labbozzetta M, Sanguedolce R, Alaimo A, Carina V, Maurici A, Cusimano A, Cervello M, D'Alessandro N. (literal)
Pagina inizio
  • 923 (literal)
Pagina fine
  • 930 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 28 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 4 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Scienze Farmacologiche, Università di Palermo, Via del Vespro 129, I-90127 Palermo; IBIM C.N.R. 'Alberto Monroy', Via U. La Malfa 153, I-90146 Palermo, Italy (literal)
Titolo
  • Antitumor effects of the novel NF-kappa B inhibitor dehydroxymethyl-epoxyquinomicin on human hepatic cancer cells: Analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production (literal)
Abstract
  • We tested the novel NF-kappa B inhibitor dehydroxy-methylepoxyquinomicin (DHMEQ) in the hepatic cancer (HCC) HepG2, HA22T/VGH and HuH-6 cells. The sensitivity to the cell growth inhibitory and apoptotic effects of the agent increased along with the levels of constitutively activated NF-kappa B, which were low in HepG2 and higher in HA22T/VGH and HuH-6. In HA22T/VGH, DHMEQ exhibited synergy with cisplatin. In the same cells, DHMEQ exerted dose-dependent decreases in the nuclear levels of activated NF-kappa B and attenuated NF-kappa B activation by cisplatin. It down-regulated Bcl-X-L mRNA in a dose-dependent manner and up-regulated that of Bcl-X-S. It also decreased interleukin 6 (IL-6), NAIP and, after 16 h of exposure to the higher concentration tested (10 mu g/ml), c-IAP-1 mRNA levels. At 10 mu g/ml it caused significant increase in Bax, XIAP, cyclin D1 and beta-catenin mRNAs. The combination of DHMEQ with cisplatin produced unexpected significant decrease in c-IAP-2 and Bcl-X-S mRNAs as well as additive decrease (IL-6, NAIP and, after 16 h, Bcl-X-L) or increase (XIAP at 8 h) in gene expression. HA22T/VGH produce IL-6; in agreement with the results on mRNA, DHMEQ inhibited such a process. HA22T/VGH lack the IL-6 receptor alpha chain, ruling out that in these cells the antitumor effects of DBMEQ may be attributed to an interference with a growth stimulatory autocrine loop based on IL-6. However, the use of DHMEQ in HCC might be beneficial to contrast the adverse systemic effects of the released cytokine. (literal)
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