4-(Tert-butyl)-2,6-bis(1-phenylethyl)phenol induces pro-apoptotic activity.
4-(Tert-butyl)-2,6-bis(1-phenylethyl)phenol induces pro-apoptotic activity.
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DOI：
10.4196/kjpp.2016.20.3.253
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Cho JY
中科院分区：
文献类型：
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作者：
Kim JH;Lee Y;Kim MY;Cho JY
在此之前，我们发现从球孢虫草的丁醇级分（Cb-BF）中分离的KTH-13显示出抗癌活性。为了提高其抗增殖活性和产量，我们采用全合成方法和衍生化KTH-13以获得化学类似物。本研究选择KTH-13衍生物4-（叔丁基）-2，6-双（1-苯乙基）苯酚（KTH-13-t-Bu）进行抗癌活性的研究。KTH-13-t-Bu抑制C6胶质瘤、MDA-MB-231、LoVo和HCT-15细胞的增殖。KTH-13-t-Bu以剂量依赖性方式诱导C6胶质瘤细胞的形态学变化。KTH-13-t-Bu还增加了用annexin V-FITC染色的早期凋亡细胞的水平。此外，KTH-13-t-Bu增加了裂解的半胱天冬酶-3和-9的水平。相比之下，KTH-13-t-Bu上调胱天蛋白酶-3、-8和-9和Bcl-2的原形式和切割形式的水平。磷酸-STAT 3、磷酸-Src和磷酸-AKT水平也通过KTH 13-t-Bu处理降低。因此，这些结果强烈表明KTH-13-t-Bu可被认为是一种具有促细胞凋亡活性的新型抗癌药物。
Previously, we found that KTH-13 isolated from the butanol fraction of Cordyceps bassiana (Cb-BF) displayed anti-cancer activity. To improve its antiproliferative activity and production yield, we employed a total synthetic approach and derivatized KTH-13 to obtain chemical analogs. In this study, one KTH-13 derivative, 4-(tert-butyl)-2,6-bis(1-phenylethyl)phenol (KTH-13-t-Bu), was selected to test its anti-cancer activity. KTH-13-t-Bu diminished the proliferation of C6 glioma, MDA-MB-231, LoVo, and HCT-15 cells. KTH-13-t-Bu induced morphological changes in C6 glioma cells in a dose-dependent manner. KTH-13-t-Bu also increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, KTH-13-t-Bu increased the levels of cleaved caspase-3 and -9. In contrast, KTH-13-t-Bu upregulated the levels of pro- and cleaved forms of caspase-3, -8, and -9 and Bcl-2. Phospho-STAT3, phospho-Src, and phospho-AKT levels were also diminished by KTH13-t-Bu treatment. Therefore, these results strongly suggest that KTH-13-t-Bu can be considered a novel anti-cancer drug displaying pro-apoptotic activity.