Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced by 1,25-dihydroxyvitamin D3 and retinoic acid.
Magnolol (MG) and honokiol (HK), two lignans showing anti-inflammatory and anti-oxidant properties and abundantly available in the medicinal plants Magnolia officinalis and M. obovata, were found to enhance HL-60 cell differentiation initiated by low doses of 1,25-dihydroxyvitamin D3 (VD3) and all-trans-retinoic acid (ATRA). Cells expressing membrane differentiation markers CD11b and CD14 were increased from 4% in non-treated control to 8-16% after being treated with 10-30 microM MG or HK. When added to 1 nM VD3, MG or HK increased markers expressing cells from approximately 30% to 50-80%. When either MG or HK was added to 20 nM ATRA, only CD11b, but not CD14, expressing cells were increased from 9% to 24-70%. Under the same conditions, adding MG or HK to VD3 or ATRA treatment further enlarged the G0/G1 cell population and increased the expression of p27(Kip1), a cyclin-dependent kinase inhibitor. Pharmacological studies using PD098059 (a MEK inhibitor), SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK inhibitor) suggested that the MEK pathway was important for VD3 and ATRA-induced differentiation and also its enhancement by MG or HK, the p38 MAPK pathway had a inhibitory effect and the JNK pathway had little influence. It is evident that MG and HK are potential differentiation enhancing agents which may allow the use of low doses of VD3 and ATRA in the treatment for acute promyelocytic leukemia.
Bioactive Products Research Group, Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong SAR, China. bhwffong@cityu.edu.hk
Wang-Fun
WF
Fong
Anfernee Kai-Wing
AK
Tse
Ka-Hung
KH
Poon
Cheng
C
Wang
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D039481:CD11b Antigen / Q000096:biosynthesis; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D000498:Allyl Compounds; D010636:Phenols
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D039481:CD11b Antigen; D002117:Calcitriol; D002120:Calcium Channel Agonists; D017705:Lignans; D018950:Lipopolysaccharide Receptors; D014212:Tretinoin; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols