Cell cycle phase-dependent effect of retinoic acid on the induction of granulocytic differentiation in HL-60 promyelocytic leukemia cells. Evidence for sphinganine potentiation of retinoic acid-induced differentiation.
The efficiency of retinoic acid (RA)-induced differentiation was dependent on the position of HL-60 cells in the cell cycle. Our results demonstrated that cells at the G1/S border were more efficiently induced to differentiate by short exposure to RA than cells at other phases of the cell cycle. Synchronization of cells in G1/S phase by aphidicolin (APH) or mimosine (MIMO) increased the sensitivity of cells to RA short exposure treatment. Pretreatment with sphinganine (SP), a protein kinase C (PKC) inhibitor, potentiated RA-induced cell differentiation. By cell cycle analysis, SP was found to block the cell progression through the G1/S phase. Consequently, cells accumulated in the G1/S phase of the cell cycle. The present data therefore suggest a possible mechanism of action of SP to enhance RA-induced differentiation.
Hui
E K
EK
Department of Pharmacology, Chang Gung Medical College, Taiwan, Republic of China.
Yung
B Y
BY
D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000473:pathology; D008898:Mimosine / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016590:Aphidicolin; D008898:Mimosine; D014212:Tretinoin; D012313:RNA; D004247:DNA; D013110:Sphingosine; C005682:safingol