title: Growth inhibition and induction of apoptosis and differentiation of tanshinone IIA in human glioma cells.
abstract: Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic activities against multiple human cancer cells, inducing apoptosis and differentiation of some human cancer cells. The purpose of this study is to confirm its anticancer activity on human glioma cells, and to elucidate mechanism of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its effect of apoptosis induction was detected through EB/AO staining, cell cycle analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation induction effect was investigated through morphology, mRNA and protein expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of tanshinone IIA, the apoptotic cells increased significantly (P < 0.01), the cells in G(0)/G(1) phase increased (P < 0.01), and decreased in S phase, ADPRTL1 and CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and protein expressions increased, nestin mRNA and protein expressions decreased significantly. The findings in this study suggested that tanshinone IIA exhibited strong effects on growth inhibition and induction of apoptosis and differentiation in human glioma cells. It might serve as a novel promising differentiation-inducing and/or therapeutic agent for human gliomas, and need to be investigated further.
authors.affiliation: Division of Experimental Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiujie
authors.initials: X
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Jiang
authors.forename: Shulan
authors.initials: S
authors.lastname: Yuan
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhujuan
authors.initials: Z
authors.lastname: Xiong
authors.forename: Yaying
authors.initials: Y
authors.lastname: Wu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ren
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yang
mesh_terms: D045784:Abietanes; D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D010616:Phenanthrenes; D012333:RNA, Messenger; C021751:tanshinone