Magnolol inhibits human glioblastoma cell proliferation through upregulation of p21/Cip1.
Previously, we demonstrated that magnolol isolated from the bark of Magnolia officinalis has anticancer activity in colon, hepatoma, and leukemia cell lines. In this study, we show that magnolol concentration dependently (0-40 microM) decreased the cell number in a cultured human glioblastoma cancer cell line (U373) and arrested the cells at the G0/G1 phase of the cell cycle. Magnolol treatment decreased the protein levels of cyclins A and D1 and increased p21/Cip1, but not cyclins B and D3, cyclin-dependent kinase (CDK)2, CDK4, CDC25C, Weel, p27/Kip1, and p53. The CDK2-p21/Cip1 complex was increased, and the CDK2 kinase activity was decreased in the magnolol-treated U373. Pretreatment of U373 with p21/Cip1 specific antisense oligodeoxynucleotide prevented the magnolol-induced increase of p21/Cip1 protein levels and the decrease of DNA synthesis. Magnolol at a concentration of 100 microM induced DNA fragmentation in U373. Our findings suggest the potential applications of magnolol in the treatment of human brain cancers.
Chen
Li-Ching
LC
Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, Taipei, Taiwan.
Liu
Yu-Chi
YC
Liang
Yu-Chih
YC
Ho
Yuan-Soon
YS
Lee
Wen-Sen
WS
D001713:Biphenyl Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*
D001713:Biphenyl Compounds; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017705:Lignans; D010936:Plant Extracts; C005498:magnolol