Enhancement of 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced HL-60 leukemia cell differentiation by Panax ginseng.
Ginseng (Panax ginseng C.A. Meyer) has a wide range of therapeutic uses including cancer treatment. Human promyelocytic leukemia cells differentiate into monocytes or granulocytes when treated with 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] or all-trans retinoic acid (ATRA). Treatment of HL-60 cells with zero to 100 microg/ml of a methanol extract of ginseng for 72 h induced a small increase in cell differentiation. Surprisingly, a synergistic induction of differentiation was observed when HL-60 cells were treated with ATRA or 1,25-(OH)(2)D(3) and the extract. The inhibitors of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK), but not of phosphoinositide 3-kinase (PI3-K), inhibited the HL-60 differentiation induced by the extract in combination with ATRA or 1,25-(OH)(2)D(3), signifying that PKC and ERK were involved in the cell differentiation enhancement by the extract. These results suggest that the ability of a methanol extract of ginseng to enhance the differentiation potential of ATRA or 1,25-(OH)(2)D(3) may improve the ultimate outcome of acute promyelocytic leukemia therapy.
School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Seung-Hyun
SH
Kim
Seung-Sik
SS
Cho
Jaya-Ram
JR
Simkhada
Hyo-Jeong
HJ
Lee
Si-Wouk
SW
Kim
Tae-Sung
TS
Kim
Jin-Cheol
JC
Yoo
D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D000432:Methanol / Q000737:chemistry; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D014212:Tretinoin; D002117:Calcitriol; D000432:Methanol