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Your search keyword '"R. Sanguedolce"' showing total 2 results
Start Over Author "R. Sanguedolce" Journal international journal of oncology
2 results on '"R. Sanguedolce"'

1. 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

Author

R. Sanguedolce, Alessandra Alaimo, Valeria Carina, Melchiorre Cervello, Natale D'Alessandro, Annamaria Maurici, Paola Poma, Manuela Labbozzetta, Antonella Cusimano, and Monica Notarbartolo

Subjects
Cisplatin, Cancer Research, medicine.medical_specialty, Oncogene, Cell growth, medicine.medical_treatment, Biology, XIAP, Endocrinology, Cytokine, Oncology, Apoptosis, Internal medicine, Cancer cell, medicine, Cancer research, Autocrine signalling, medicine.drug
Abstract

We tested the novel NF-kappaB 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-kappaB, 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-kappaB and attenuated NF-kappaB 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 microg/ml), c-IAP-1 mRNA levels. At 10 microg/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-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.

Published
2006
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2. Antitumor effects of the novel NF-kappaB 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.

Author

Poma P, Notarbartolo M, Labbozzetta M, Sanguedolce R, Alaimo A, Carina V, Maurici A, Cusimano A, Cervello M, and D'Alessandro N

Subjects
Antineoplastic Agents pharmacology, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Cell Nucleus drug effects, Cell Nucleus metabolism, Cell Survival drug effects, Cell Survival genetics, Cisplatin pharmacology, Dose-Response Relationship, Drug, Drug Synergism, Gene Expression drug effects, HeLa Cells, Humans, Inhibitor of Apoptosis Proteins genetics, Interleukin-6 biosynthesis, Liver Neoplasms genetics, Liver Neoplasms metabolism, Liver Neoplasms pathology, NF-kappa B metabolism, Neuronal Apoptosis-Inhibitory Protein genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, bcl-X Protein genetics, Benzamides pharmacology, Cyclohexanones pharmacology, NF-kappa B antagonists & inhibitors
Abstract

We tested the novel NF-kappaB 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-kappaB, 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-kappaB and attenuated NF-kappaB 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 microg/ml), c-IAP-1 mRNA levels. At 10 microg/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-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.

Published
2006

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