Prostate Cancer Scientific Abstracts - L

Welcome to the Prostate Cancer Guide scientific abstracts, author section L. Here you will find abstracts from the latest research being carried out in the field.

This section is recommended for people who have a scientific interest in prostate cancer. It is recommended that people without prior knowledge of prostate cancer visit the more general areas of the site (Prostate Cancer Guide).

Abstract Authors


Latest Prostate Cancer Abstract

Journal: International Journal of Cancer.

Issue: 2006, 119(1):221-8.

Pubmed ID: 16450389

Authors: Lakshmikanthan V, Kaddour-Djebbar I, Lewis RW, Kumar MV.

Title: suberolylanilide hydroxamic acid-sensitized prostate cancer cells to TNFalpha-related apoptosis-inducing ligand (TRAIL): Mechanisms leading to synergistic apoptosis.

Treatment of cancer cells with histone deacetylase inhibitors such as suberolylanilide hydroxamic acid activates genes that promote apoptosis. To enhance proapoptotic efficiency, suberolylanilide hydroxamic acid has been used in combination with radiation, kinase inhibitors and cytotoxic drugs. Although several prostate cells respond to TNFalpha-Related Apoptosis-Inducing Ligand (TRAIL), LNCaP are resistant. This model system was utilized to examine the advantages of combined treatment with suberolylanilide hydroxamic acid and TRAIL. In LNCaP cells, TRAIL induced synergistic apoptosis when combined with even with the lowest dose suberolylanilide hydroxamic acid. Treatment with caspase inhibitor confirmed that suberolylanilide hydroxamic acid-induced apoptosis was mediated through caspases. In addition to induction of apoptosis, suberolylanilide hydroxamic acid and TRAIL decreased the levels of proapoptotic proteins IKKalpha, IKKbeta and IKKgamma, suggesting that suberolylanilide hydroxamic acid treatment may reduce the activity of NFkappaB. However, assay for NFkappaB luciferase reporter activity showed highly significant increase in suberolylanilide hydroxamic acid-treated cells, supporting earlier suggestions that histone deacetylase inhibitors promotes NFkappaB transcriptional activity. Further analyses to determine the mechanisms by which the combination of suberolylanilide hydroxamic acid and TRAIL led to synergistic apoptosis indicated that the apoptotic response of LNCaP is due to a complex regulation of death receptor pathway and alterations of NFkappaB activity at several regulatory steps.

Contact: Department of Surgery, Medical College of Georgia, Augusta, GA.

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