Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway

Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway
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厚朴酚通过p53途径抑制胆囊癌细胞的生长

DOI:
10.1111/cas.12762
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发表时间:
2015-10-01
期刊:
影响因子:
5.7
通讯作者:
Liu, Yingbin
Liu, Yingbin
中科院分区:
医学2区
文献类型:
--
作者:
Li, Maolan;Zhang, Fei;Liu, Yingbin

文献摘要

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厚朴酚是厚朴中的主要活性成分,具有抗炎、抗氧化作用,临床应用广泛。本研究探讨厚朴酚对人胆囊癌细胞株生长的影响。结果表明,厚朴酚对胆囊癌细胞株的生长有明显的抑制作用,且呈剂量和时间依赖性。厚朴酚还通过上调p53和p21蛋白水平,下调cyclin D1、CDC 25 A和Cdk 2蛋白水平,将细胞周期进程阻滞在G(0)/G(1)期,并诱导与肿瘤相关的凋亡。当细胞用p53抑制剂(pifithrin-a)预处理,然后用厚朴酚处理时,pifithrin-a阻断厚朴酚诱导的凋亡和G(0)/G(1)阻滞。在体内,厚朴酚抑制肿瘤生长,并激活与体外激活相同的机制。总之,我们的研究是第一个报告,厚朴酚对GBC细胞的生长有抑制作用,这种化合物可能有潜力作为一种新的治疗剂,用于治疗GBC。
Magnolol, the major active compound found in Magnolia officinalis has a wide range of clinical applications due to its anti-inflammation and anti-oxidation effects. This study investigated the effects of magnolol on the growth of human gallbladder carcinoma (GBC) cell lines. The results indicated that magnolol could significantly inhibit the growth of GBC cell lines in a dose- and time-dependent manner. Magnolol also blocked cell cycle progression at G(0)/G(1) phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. When cells were pretreated with a p53 inhibitor (pifithrin-a), followed by magnolol treatment, pifithrin-a blocked magnolol-induced apoptosis and G(0)/G(1) arrest. In vivo, magnolol suppressed tumor growth and activated the same mechanisms as were activated in vitro. In conclusion, our study is the first to report that magnolol has an inhibitory effect on the growth of GBC cells and that this compound may have potential as a novel therapeutic agent for the treatment of GBC.