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Regulation of cell cycle and apoptosis by protein kinase C in rat myeloid leukemia cell line.

Abstract
The role of protein kinase C (PKC) in regulation of the cell cycle and induction of apoptosis was examined in a rat myeloid leukemia cell line--chloroma. Exposure of chloroma cells to calphostin C (a specific PKC inhibitor) led to inhibition of cell proliferation, caused by (i) partial and transient arrest of cells in the G1 phase of the cell cycle and (ii) induction of apoptosis in part of the cell population. The calphostin-C-induced inhibition of PKC activity was accompanied by changes in the expression of proliferating cell nuclear antigen (PCNA)--a protein known to participate in regulation of DNA replication and repair. Flow cytometry and western blot analyses of the PCNA expression showed that, following the calphostin C treatment, expression of PCNA declined and attained the lowest value on day 2, followed by recovery to the control level. The decline of the PCNA expression was accompanied by changes in the molecular weight of the protein suggesting either its degradation or release of unfinished protein. The decline/recovery of the PCNA expression followed the same time-pattern as the cell cycle arrest and apoptosis. Cell apoptosis is often accompanied by cell cycle arrest, therefore, we further examined whether G1 arrest would, by itself, cause apoptosis. Exposure of the chloroma cells to various doses of hydroxyurea, a G1 arrest inducing agent, caused cell apoptosis within 24-48 h after treatment. This suggests that PKC might indirectly be responsible for the chloroma cell apoptosis induced by calphostin C. In conclusion, it appears that PKC regulates cell cycle progression by modulating the G1 to S phase transition. One of the possible targets of the PKC effects observed here might be, among others (?), PCNA--a protein involved in regulation of both cell proliferation and apoptosis.
AuthorsD Leszczynski
JournalOncology research (Oncol Res) Vol. 7 Issue 9 Pg. 471-80 ( 1995) ISSN: 0965-0407 [Print] United States
PMID8835291 (Publication Type: Journal Article)
Chemical References
  • Enzyme Inhibitors
  • Naphthalenes
  • Proliferating Cell Nuclear Antigen
  • calphostin complex
  • DNA
  • Protein Kinase C
  • Hydroxyurea
Topics
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Cycle (physiology)
  • Cell Division (drug effects)
  • DNA (chemistry)
  • Enzyme Inhibitors (pharmacology)
  • Flow Cytometry
  • Hydroxyurea (pharmacology)
  • Immunoenzyme Techniques
  • Interphase (drug effects)
  • Leukemia, Myeloid (drug therapy, pathology)
  • Naphthalenes (pharmacology)
  • Proliferating Cell Nuclear Antigen (biosynthesis)
  • Protein Kinase C (antagonists & inhibitors, metabolism)
  • Rats
  • Repetitive Sequences, Nucleic Acid
  • S Phase (drug effects)
  • Time Factors
  • Tumor Cells, Cultured

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