TY - JOUR
T1 - Differential involvement of protein kinase C in human promyelocytic leukemia cell differentiation enhanced by artemisinin
AU - Kim, Seung Hyun
AU - Kim, Hyeong Joon
AU - Kim, Tae Sung
N1 - Funding Information:
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ10-PG6-01GN16-0005).
PY - 2003/12/15
Y1 - 2003/12/15
N2 - Artemisinin, a sesquiterpene lactone endoperoxide that exists in several medicinal plants, is a well-known anti-malarial agent. In this report, we investigated the effect of artemisinin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Artemisinin markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with low doses of 1α,25-dihydoxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (all-trans RA). Artemisinin by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that artemisinin potentiated 1,25-(OH)2D3-induced cell differentiation predominantly into monocytes and all-trans RA-induced cell differentiation into granulocytes, respectively. Extracellular-regulated kinase (ERK) inhibitors markedly inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH)2D3 or all-trans RA, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitors did not. Particularly, protein kinase C (PKC) inhibitors inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH) 2D3 but not with all-trans RA. Artemisinin enhanced PKC activity and protein level of PKCβI isoform in only 1,25-(OH) 2D3-treated HL-60 cells. Taken together, these results indicate that artemisinin strongly enhanced 1,25-(OH)2D3- and all-trans RA-induced cell differentiation in which PKC is differentially involved in arteminisin-mediated enhancement of leukemia cell differentiation.
AB - Artemisinin, a sesquiterpene lactone endoperoxide that exists in several medicinal plants, is a well-known anti-malarial agent. In this report, we investigated the effect of artemisinin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Artemisinin markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with low doses of 1α,25-dihydoxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (all-trans RA). Artemisinin by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that artemisinin potentiated 1,25-(OH)2D3-induced cell differentiation predominantly into monocytes and all-trans RA-induced cell differentiation into granulocytes, respectively. Extracellular-regulated kinase (ERK) inhibitors markedly inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH)2D3 or all-trans RA, whereas phosphatidylinositol 3-kinase (PI3-K) inhibitors did not. Particularly, protein kinase C (PKC) inhibitors inhibited HL-60 cell differentiation induced by artemisinin in combination with 1,25-(OH) 2D3 but not with all-trans RA. Artemisinin enhanced PKC activity and protein level of PKCβI isoform in only 1,25-(OH) 2D3-treated HL-60 cells. Taken together, these results indicate that artemisinin strongly enhanced 1,25-(OH)2D3- and all-trans RA-induced cell differentiation in which PKC is differentially involved in arteminisin-mediated enhancement of leukemia cell differentiation.
KW - Artemisinin
KW - Cell differentiation
KW - ERK (extracellular-regulated kinase)
KW - Leukemia
KW - PKC (protein kinase C)
UR - http://www.scopus.com/inward/record.url?scp=0345599966&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2003.09.057
DO - 10.1016/j.ejphar.2003.09.057
M3 - Article
C2 - 14660006
AN - SCOPUS:0345599966
SN - 0014-2999
VL - 482
SP - 67
EP - 76
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -