Butyrate-Induced Apoptosis in Prostate Cancer Cell Lines
Abstract
This project was aimed toward characterizing prostate cancer cell lines for responses to butyrate, and determining molecular determinants of sensitivity to butyrate-induced growth termination. Each of three prostate cancer cell lines, DU145, PC3 and LNCaP, exhibited persistent inhibition of growth after a 2 day treatment with butyrate. Most interestingly, the PC3 cell line ceased replicating but did not die, while LNCaP and DU145 underwent an initial wave of cell death. The PC3 cell could be protected from this persistent growth arrest by coculture with bone stroma, an effect also seen in a variant that exhibited enhanced growth in the absence of stroma. An additional form of butyrate response was seen in derivatives of the T24 bladder cancer cell line, which exhibit delayed onset apoptosis during butyrate treatment. Several lines of evidence pointed to a cyclin-independent role for p21cip1 protein in the ability of prostate cancer cell lines and T24 derivatives to tolerate butyrate treatment. Most remarkably, the JCA1 variant of T24 continued to divide mitotically during butyrate treatment, arresting in the subsequent G1phase. Such arrest was however unstable, the cultures reinitiating DNA replication over the next 40 hr in association with declining level p21cip1, increasing level of cyclin E and increasing incidence of apoptosis. A comparable phenomenon in the G2 arrest competent T24 variant, TSUPr1, suggests that butyrate-induced apoptosis was independent of cell cycle phase.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADB283780
Entities
People
- John A. Mcbain
Organizations
- Dartmouth College