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芳樟醇通过上调 p53 和细胞周期蛋白依赖性激酶抑制剂优先诱导多种白血病细胞发生强烈的细胞凋亡。

Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors.

机构信息

Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

出版信息

Toxicology. 2010 Jan 31;268(1-2):19-24. doi: 10.1016/j.tox.2009.11.013. Epub 2009 Nov 14.

Abstract

Linalool, a natural small molecule monoterpene, has been shown to have anti-tumor activity against several human tumor cell lines in vitro; however, the anti-leukemia spectrum and molecular mechanisms inhibiting tumor cell growth are not fully understood. In the present study, we demonstrated that linalool preferentially induced growth arrest and apoptosis of a variety of human leukemia cells, but spared normal hematopoietic cells. Treatment of leukemia cells by linalool for 12h led to strong activation of p53, cyclin-dependent kinase inhibitors (CDKIs), GADD45alpha, c-jun and phosphorylated-JNK, suggesting that linalool-induced apoptosis might be associated with activation of p53 and CDKIs. The findings here warrant further investigation of this class of natural product as lead compound for developing novel therapeutic agents for leukemia.

摘要

芳樟醇是一种天然的小分子单萜,已被证明在体外对几种人肿瘤细胞系具有抗肿瘤活性;然而,抑制肿瘤细胞生长的抗白血病谱和分子机制尚不完全清楚。在本研究中,我们证明芳樟醇优先诱导多种人白血病细胞的生长停滞和凋亡,但对正常造血细胞无影响。芳樟醇处理白血病细胞 12 小时可导致 p53、细胞周期蛋白依赖性激酶抑制剂 (CDKIs)、GADD45alpha、c-jun 和磷酸化-JNK 的强烈激活,提示芳樟醇诱导的凋亡可能与 p53 和 CDKIs 的激活有关。这些发现为将此类天然产物作为开发新型白血病治疗药物的先导化合物进一步研究提供了依据。

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