TY - JOUR
T1 - Potentiation of 1,25-dihydroxyvitamin D3-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone
AU - Kim, Seung H.
AU - Kang, So N.
AU - Kim, Hyeoung J.
AU - Kim, Tae S.
N1 - Funding Information:
We would like to thank Y.C. Lee, S.Y. Chun, and J.H. Cheong (all with Chonnam National University, Korea) for providing valuable reagents and instruments. This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Wealfare, Republic of Korea (01-PJ10-PG6-01GN16-005).
PY - 2002/10/15
Y1 - 2002/10/15
N2 - Costunolide, a germacranolide sesquiterpene lactone that exists in several medicinal plants, is known to be a possible anti-cancer and chemopreventive agent for tumorigenesis. In this report, we investigated the effect of costunolide on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5 nM 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Costunolide by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that costunolide potentiated 1,25-(OH)2D3-induced cell differentiation predominantly into monocytes. Inhibitors for PKC, PI3-K, and ERK markedly inhibited HL-60 cell differentiation induced by costunolide in combination with 1,25-(OH)2D3. In addition, pretreatment of HL-60 cells with costunolide before the 1,25-(OH)2D3 addition also potentiated cell differentiation in a concentration- and time-dependent manner, and the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-κB-binding activity by costunolide. These results indicate that PKC, PI3-K, ERK and NF-κB may be involved in 1,25-(OH)2D3-mediated cell differentiation enhanced by costunolide.
AB - Costunolide, a germacranolide sesquiterpene lactone that exists in several medicinal plants, is known to be a possible anti-cancer and chemopreventive agent for tumorigenesis. In this report, we investigated the effect of costunolide on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5 nM 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Costunolide by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that costunolide potentiated 1,25-(OH)2D3-induced cell differentiation predominantly into monocytes. Inhibitors for PKC, PI3-K, and ERK markedly inhibited HL-60 cell differentiation induced by costunolide in combination with 1,25-(OH)2D3. In addition, pretreatment of HL-60 cells with costunolide before the 1,25-(OH)2D3 addition also potentiated cell differentiation in a concentration- and time-dependent manner, and the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-κB-binding activity by costunolide. These results indicate that PKC, PI3-K, ERK and NF-κB may be involved in 1,25-(OH)2D3-mediated cell differentiation enhanced by costunolide.
KW - 1,25-Dihydroxyvitamin D
KW - Cell differentiation
KW - Costunolide
KW - Extracellular signal-regulated kinase
KW - Nuclear factor-κB
KW - Protein kinase C
UR - http://www.scopus.com/inward/record.url?scp=0037107596&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(02)01292-3
DO - 10.1016/S0006-2952(02)01292-3
M3 - Article
C2 - 12234604
AN - SCOPUS:0037107596
SN - 0006-2952
VL - 64
SP - 1233
EP - 1242
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 8
ER -
