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Emodin induces apoptosis of cancer cells and inhibits retinoid X receptor transcriptional activity
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 4
- DOI:
- 10.3321/j.issn:0513-4870.2008.04.004
- Key Word:
- 大黄素;维甲酸受体;肝肿瘤;肺肿瘤;细胞凋亡
Abstract： 大黄素(emodin)对多种肿瘤细胞有较强的抑制增殖和诱导凋亡的作用,但其作用机制尚不清楚.本研究通过配体-受体竞争结合实验以及报告基因检测了大黄素对维甲酸X受体(retinoid X receptor alpha,RXRα)的结合和转录活性的调控,并研究了大黄素对肺癌细胞H460和肝癌细胞SMMC-7721生长和凋亡的作用.结果发现,大黄素对两种癌细胞有很强的抑制增殖作用,加入RXRα的天然配体9-顺式视黄酸(9-cis-retinoid acid,9-cis-RA)共同处理可显著缓解这种抑制作用.大黄素能浓度依赖地引起两种癌细胞系的凋亡,使细胞核出现碎裂和染色质浓染.报告基因实验发现大黄素对RXRα同源和异源二聚体的转录激活有显著抑制作用.体外的配体竞争结合实验发现,大黄素不直接结合RXRα的配体结合区.蛋白质免疫印迹实验发现,大黄素不影响RXRα的蛋白表达.结果提示,大黄素具有诱导肺癌细胞H460和肝癌细胞SMMC-7721凋亡和抑制细胞生长的作用,大黄素抑制9-cis-RA对RXR转录激活作用以及9-cis-RA具有一定程度拮抗大黄素对肺癌细胞H460和肝癌细胞SMMC-7721的生长抑制作用,提示大黄素的抗癌作用可能与细胞内RXR的功能有关,并以RXR转录非依赖性的方式起作用.配体竞争结合实验结果提示大黄素可能间接作用于RXR.
- [1]X K, Zhang,B, Hoffmann,P B, Tran,etc.Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.[J].1992,355(6359).
- [2]R, Mukherjee,P J, Davies,D L, Crombie,etc.Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists.[J].1997,386(6623).
- [3]R M, Evans.The steroid and thyroid hormone receptor superfamily.[J].1988,240.
- [4]R A, Heyman,D J, Mangelsdorf,J A, Dyck,etc.9-cis retinoic acid is a high affinity ligand for the retinoid X receptor.[J].1992,68(2).
- [5]A A, Levin,L J, Sturzenbecker,S, Kazmer,etc.9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha.[J].1992,355.
- [6]Mangelsdorf, D.J.,Ong, E.S..Nuclear receptor that identifies a novel retinoic acid response pathway.[J].1990,345(6272).
- [7]X K, Zhang,J, Lehmann,B, Hoffmann,etc.Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.[J].1992,358(6387).
- [8]Karunagaran D,Vidhyalakshmi S,Senan VP,etc.Emodin induces apoptosis of human cervical cancer cells through poly(ADP-ribose) polymerase cleavage and activation of caspase-9.[J].2003,473(2).
- [9]Maripat Corr,Xiao-kun Zhang,Siva Kumar Kolluri,etc.The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis[J].2005,102(7).
- [10]Chiang LC.,Lin CC.,Chen YY.,etc.Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells[J].2004,74(18).
- [11]Saitoh A,Muto A,Asakura K,etc.Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor.[J].2007,6(3).