Molecular mechanisms of cell cycle block by methionine restriction in human prostate cancer cells
Abstract
Previous studies have shown that dietary or pharmacological methionine restriction inhibits growth of human prostate cancer cells in vitro or as xenografts in mice. We undertook the present studies to clarify the molecular mechanisms by which methionine restriction inhibits prostate cancer cell growth. We found that PC-3 and DU 145 cells stopped proliferating within six days in growth medium containing homocysteine in place of methionine. In contrast, proliferation of LNCaP cells was only partially inhibited by the absence of methionine. Using flow cytometry, we found that methionine restriction caused PC-3 cells to arrest in all phases of the cell cycle, but predominantly in the G2/M phase, whereas LNCaP cells accumulated exclusively in the G1 phase. Methionine restriction led to accumulation of the cyclin-dependent kinase inhibitors p21 and p27, as determined by Western blot analysis, and inhibited the enzymatic activities of the cyclin-dependent kinases CDK2 and cdc2, as determined by an in vitro kinase assay: However, methionine restriction had little or no effect on CDK2 or cdc2 protein levels. Methionine restriction also induced PC-3 cells to undergo apoptosis, as indicated by the appearance of a typical nucleosomal ladde...Continue Reading
References
Citations
Related Concepts
Related Feeds
Cell Cycle Pathways
Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.
Cell Checkpoints & Regulators
Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis