Butyrate-Induced Apoptosis in Prostate Cancer Cells
Abstract
This study aims to determine common features of the response to butyrate, an inhibitor of histone deacetylase, by prostate cancer cell lines. One issue of prime importance is the range of cell phenotypes of susceptible and resistant cell%lines. Three out of five poorly differentiated prostate cancer cell lines were nearly fully sensitive to terminal loss of replicative abilities after %8 hr exposure, conditions that are well tolerated by most normal cell types. Addressing our principal hypothesis, that the prototypical butyrate-hypersensitive cell will be undifferentiated and mutant in p53, we will select cell lines that are tolerant of butyrate, determine their p53 functional status (transcriptional response to ionizing radiation) and, if wild type, knock out their p53 protein using an appropriate oncoprotein. We expect that loss of p53 function will confer butyrate hypersensitivity. The work will also address the responsiveness to mezerein, an activator of protein kinase C that increases the proportion of butyrate-sensitive cells that undergo apoptosis in a 24 hr exposure. This agent is an inducer of terminal differentiation in its own right, affecting moderately differentiated adenocarcinoma cell lines. Because such lines are rare among prostate cancer cell lines (in contrast to their abundance as human cancers), this promising agent cannot be adequately studied at the present time.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1999
- Accession Number
- ADA384360
Entities
People
- John A. Mcbain
Organizations
- Dartmouth College