芸香提取物诱导DNA损伤途径并阻断Akt激活，以抑制癌细胞增殖和存活。
Ruta graveolens extract induces DNA damage pathways and blocks Akt activation to inhibit cancer cell proliferation and survival.
作者信息
Fadlalla Khalda, Watson Angela, Yehualaeshet Teshome, Turner Timothy, Samuel Temesgen
机构信息
Department of Pathobiology, Center for Cancer Research, Tuskegee, AL 36088, USA.
出版信息
Anticancer Res. 2011 Jan;31(1):233-41.
Abstract
BACKGROUND
Ruta graveolens is a medicinal herb that has been used for centuries against various ailments. This study examined the anticancer properties of the herb using cancer cell lines.
MATERIALS AND METHODS
Methanolic extract of R. graveolens was tested on colon, breast and prostate cancer cells. Viability, cell cycle profiles, clonogenicity and capase activation were measured. Induction and subcellular localizations of p53, 53BP1 and γ-H2AX proteins were examined.
RESULTS
The extract dose-dependently decreased the viability and the clonogenicity of treated cells and induced G₂/M arrest, aberrant mitoses, and caspase-3 activation. It also induced the p53 pathway and focal concentration of the DNA damage response proteins 53BP1 and γ-H2AX. Moreover, the levels of phospho-Akt and cyclin B1 were reduced by treatment, whereas only cyclin B1 was reduced in normal dermal fibroblasts.
CONCLUSION
R. graveolens extract contains bioactive compounds which, independently of known photoactivatable mechanisms, potently inhibit cancer cell proliferation and survival through multiple targets.
摘要
背景
芸香是一种药用植物，几个世纪以来一直用于治疗各种疾病。本研究使用癌细胞系检测了该植物的抗癌特性。
材料与方法
用芸香的甲醇提取物对结肠、乳腺和前列腺癌细胞进行检测。测量细胞活力、细胞周期分布、克隆形成能力和半胱天冬酶激活情况。检测p53、53BP1和γ-H2AX蛋白的诱导表达及亚细胞定位。
结果
提取物剂量依赖性地降低了处理细胞的活力和克隆形成能力，并诱导G₂/M期阻滞、异常有丝分裂和半胱天冬酶-3激活。它还诱导了p53通路以及DNA损伤反应蛋白53BP1和γ-H2AX的局部聚集。此外，处理后磷酸化Akt和细胞周期蛋白B1的水平降低，而在正常皮肤成纤维细胞中只有细胞周期蛋白B1水平降低。
结论
芸香提取物含有生物活性化合物，这些化合物独立于已知的光激活机制，通过多个靶点有效抑制癌细胞增殖和存活。
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