Cell cycle phase‐dependent effect of retinoic acid on the induction of granulocytic differentiation in HL‐60 promyelocytic leukemia cells

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Cell cycle;Granulocytic differentiation;Retinoic acid;Sphinganine;APH;aphidicolin;CAM;camptothecin;DMSO;dimethyl sulfoxide;EC;embryonal carcinoma;FBS;fetal bovine serum;MIMO;mimosine;ND;nocodazole;PBS;phosphate-buffered saline;PI;propidium iodide;PKC;protein kinase C;RA;retinoic acid;RAR;retinoic acid receptor;R point;restriction point;SP;sphinganine;ST;staurosporine;TCA;trichloroacetic acid;VIN;vinblastine