Chiara Costanzo

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We investigated the ability of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to interact with gemcitabine (GEM) in inducing pancreatic cancer cell death. The combined treatment with TSA and GEM synergistically inhibited growth of four pancreatic adenocarcinoma cell lines and induced apoptosis. This effect was associated with the induction of(More)
Pancreatic cancer is an aggressive neoplasia, and standard chemotherapies are by and large ineffective. The purpose of this work was to get a comprehensive preclinical study on the ability of anticancer drug combinations that best inhibit growth of pancreatic adenocarcinoma cells. We evaluated the in vitro growth inhibition of ten pancreatic cancer cell(More)
In cells with an altered p53 gene, the expression of p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases, can be induced by histone deacetylase (HDAC) inhibitors via a p53-independent pathway, which may play a critical role in arrest of cell growth. Accordingly, HDAC inhibitors such as trichostatin A (TSA) have potential utility in pancreatic(More)
The human IL-6 promoter contains multiple regulatory elements such as those binding transcription factors belonging to the NF-kappaB (-75/-63), C/EBP (-158/-145 and -87/-76) and AP-1 (-283/-277) families. Herein, we report that ectopic expression of c-Jun, C/EBPdelta, and the p65 subunit of NF-kappaB synergistically activates an IL-6 promoter construct(More)
Cancer cells exhibit an endogenous constitutive oxidative stress higher than that of normal cells, which renders tumours vulnerable to further reactive oxygen species (ROS) production. Mitochondrial uncoupling protein 2 (UCP2) can mitigate oxidative stress by increasing the influx of protons into the mitochondrial matrix and reducing electron leakage and(More)
We present evidence that pyrrolidine dithiocarbamate (PDTC) inhibits growth of p53-negative pancreatic adenocarcinoma cell lines via cell cycle arrest in the S-phase, while it has no effect on primary fibroblast proliferation. Growth inhibition of cancer cells is dependent on ROS and ERK1/2 induction as indicated by a significantly reduced PDTC-associated(More)
The aim of the present study was to analyse the molecular mechanisms involved in the Interleukin-6 (IL-6) silencing in pancreatic adenocarcinoma cell lines. Our results demonstrate that TNF-alpha, a major IL-6 inducer, is able to induce IL-6 only in three out of six cell lines examined. 5-aza-2'-deoxycytidine (DAC), but not trichostatin A (TSA), activates(More)
Mitochondrial uncoupling protein 2 (UCP2) can moderate oxidative stress by favoring the influx of protons into the mitochondrial matrix, thus reducing electron leakage from respiratory chain and mitochondrial superoxide production. Here, we demonstrate that UCP2 inhibition by genipin or UCP2 siRNA strongly increases reactive oxygen species (ROS) production(More)
Mammalian pancreatic ribonucleases form a family of homologous proteins that has been extensively investigated. The primary structures of these enzymes were used to derive phylogenetic trees. These analyses indicate that the presence of three strictly homologous enzymes in the bovine species (the pancreatic, seminal, and cerebral ribonucleases) is due to(More)
The histone deacetylase inhibitor trichostatin A (TSA) has been previously shown to block cellular growth in G2 and induce apoptosis in human pancreatic cancer cell lines. In order to better understand this phenomenon, we have analyzed the gene expression profiles in PaCa44 cells after treatment with TSA using microarrays containing 22,283 probesets. TSA(More)