灯盏花素通过增强半胱天冬酶-6的激活使药物诱发的结肠癌细胞凋亡敏感化。
Scutellarin sensitizes drug-evoked colon cancer cell apoptosis through enhanced caspase-6 activation.
作者信息
Chan Jason Yongsheng, Tan Benny Kwong Huat, Lee Shao Chin
机构信息
National University Medical Institutes, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
出版信息
Anticancer Res. 2009 Aug;29(8):3043-7.
BACKGROUND
We have reported that resveratrol (RSV) and 5-fluorouracil (5-FU) evoked apoptosis through caspase-6 activation in wild-type (p53+/+) and knockout (p53(-/-)) HCT116 human colon cancer cells. In this study, we investigated the sensitization effects of scutellarin (SC), a compound isolated from the traditional Chinese herb Erigeron breviscapus, on RSV and 5-FU-evoked apoptosis of these cancer cells.
MATERIALS AND METHODS
The drug-induced apoptosis was qualified by TUNEL staining under fluorescence microscopy, before being quantified by propiodium iodide staining through flow cytometric assay.
RESULTS
SC (100 microM) sensitized RSV- (200 microM) and 5-FU (500 microM)-evoked apoptosis in p53+/+ but not p53(-/-) cells. RSV- and 5-FU-elicited caspase-6 activation was promoted by SC in a time-dependent manner. SC itself did not trigger apoptosis or caspase-6 activation at the concentration tested.
CONCLUSION
SC is a novel sensitizing agent for both RSV- and 5-FU-evoked apoptosis, through the enhancement of caspase-6 activation in a p53-dependent manner.
背景
我们曾报道白藜芦醇（RSV）和5-氟尿嘧啶（5-FU）通过激活野生型（p53+/+）和基因敲除型（p53(-/-)）HCT116人结肠癌细胞中的半胱天冬酶-6引发细胞凋亡。在本研究中，我们调查了从传统中药灯盏花中分离出的化合物灯盏花素（SC）对RSV和5-FU诱导这些癌细胞凋亡的致敏作用。
材料与方法
药物诱导的细胞凋亡通过荧光显微镜下的TUNEL染色进行鉴定，然后通过碘化丙啶染色经流式细胞术检测进行定量分析。
结果
SC（100微摩尔）使RSV（200微摩尔）和5-FU（500微摩尔）诱导的p53+/+细胞凋亡致敏，但对p53(-/-)细胞无此作用。SC以时间依赖性方式促进RSV和5-FU诱导的半胱天冬酶-6激活。在所测试的浓度下，SC本身不会引发细胞凋亡或半胱天冬酶-6激活。
结论
SC是一种新型致敏剂，通过以p53依赖性方式增强半胱天冬酶-6激活，使RSV和5-FU诱导的细胞凋亡致敏。
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