Antitumor effects of the novel NF-κB 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

  • Authors:
    • Paola Poma
    • Monica Notarbartolo
    • Manuela Labbozzetta
    • Rosario Sanguedolce
    • Alessandra Alaimo
    • Valeria Carina
    • Annamaria Maurici
    • Antonella Cusimano
    • Melchiorre Cervello
    • Natale D'Alessandro
  • View Affiliations

  • Published online on: April 1, 2006     https://doi.org/10.3892/ijo.28.4.923
  • Pages: 923-930
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Abstract

We tested the novel NF-κB inhibitor dehydroxymethylepoxyquinomicin (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-κB, 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-κB and attenuated NF-κB activation by cisplatin. It down-regulated Bcl-XL mRNA in a dose-dependent manner and up-regulated that of Bcl-XS. It also decreased interleukin 6 (IL-6), NAIP and, after 16 h of exposure to the higher concentration tested (10 µg/ml), c-IAP-1 mRNA levels. At 10 µg/ml it caused significant increase in Bax, XIAP, cyclin D1 and β-catenin mRNAs. The combination of DHMEQ with cisplatin produced unexpected significant decrease in c-IAP-2 and Bcl-XS mRNAs as well as additive decrease (IL-6, NAIP and, after 16 h, Bcl-XL) 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 DHMEQ 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.

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April 2006
Volume 28 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Poma, P., Notarbartolo, M., Labbozzetta, M., Sanguedolce, R., Alaimo, A., Carina, V. ... D'Alessandro, N. (2006). Antitumor effects of the novel NF-κB 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. International Journal of Oncology, 28, 923-930. https://doi.org/10.3892/ijo.28.4.923
MLA
Poma, P., Notarbartolo, M., Labbozzetta, M., Sanguedolce, R., Alaimo, A., Carina, V., Maurici, A., Cusimano, A., Cervello, M., D'Alessandro, N."Antitumor effects of the novel NF-κB 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". International Journal of Oncology 28.4 (2006): 923-930.
Chicago
Poma, P., Notarbartolo, M., Labbozzetta, M., Sanguedolce, R., Alaimo, A., Carina, V., Maurici, A., Cusimano, A., Cervello, M., D'Alessandro, N."Antitumor effects of the novel NF-κB 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". International Journal of Oncology 28, no. 4 (2006): 923-930. https://doi.org/10.3892/ijo.28.4.923