Catechins induced acute promyelocytic leukemia cell apoptosis and triggered PML-RARα oncoprotein degradation.
Catechins induced acute promyelocytic leukemia cell apoptosis and triggered PML-RARα oncoprotein degradation.
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儿茶素诱导急性早幼粒细胞白血病细胞凋亡并引发 PML-RARα 癌蛋白降解
DOI：
10.1186/s13045-014-0075-3
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发表时间：
2014-10-01
影响因子：
28.5
通讯作者：
Zhao WL
中科院分区：
文献类型：
--
作者：
Zhang L;Chen QS;Xu PP;Qian Y;Wang AH;Xiao D;Zhao Y;Sheng Y;Wen XQ;Zhao WL
背景近来有报道称，绿色茶多酚的提取物具有预防癌症的作用。本研究探讨了绿色茶叶中天然成分儿茶素对急性早幼粒细胞白血病（APL）的作用。MTT法检测细胞活力，流式细胞仪检测细胞凋亡。Western blot检测细胞凋亡相关蛋白和PML-RARα蛋白的表达。儿茶素的体内抗肿瘤活性进行了研究，在裸鼠移植瘤与NB 4细胞和原位细胞凋亡检测由末端脱氧转移酶催化的DNA缺口末端标记assay.ResultsCatechins在微摩尔浓度水平显着抑制APL细胞增殖和诱导细胞凋亡，与线粒体损伤，活性氧产生和半胱天冬酶激活。抗凋亡Bcl-2家族成员Bcl-xL下调，促凋亡成员Bax保持不变。儿茶素诱导PML-RARα癌蛋白降解。儿茶素介导的凋亡作用也观察到原代APL细胞，而不影响正常的造血祖细胞。结论儿茶素类化合物可能通过激活内源性凋亡途径和靶向PML-RARα癌蛋白而成为治疗APL的潜在药物。
BackgroundIt has recently been reported that the extracts of green tea polyphenol have cancer preventive effects. In this study, we investigated the effect of the natural composition from green tea leaves Catechins on acute promyelocytic leukemia (APL).MethodsIn vitro, APL cell lines NB4, retinoic acid-resistant NB4-R1 and NB4-R2 were treated with different concentrations of Catechins. Cell viability and cell apoptosis were analyzed using MTT assay and flow cytometric assay, respectively. Expression of proteins related to apoptosis and PML-RARα oncoprotein were assessed by Western blot. In vivo anti-tumor activity of Catechins was examined in nude mice xenografted with NB4 cells and in situ cell apoptosis was detected by terminal deoxytransferase-catalyzed DNA nick-end labeling assay.ResultsCatechins at micromolar concentration levels significantly inhibited APL cell proliferation and induced cell apoptosis, in association with mitochondria damage, ROS production and caspase activation. The anti-apoptotic Bcl-2 family member Bcl-xL was down regulated, with pro-apoptotic member Bax remaining unchanged. Moreover, Catechins induced the degradation of PML-RARα oncoprotein. Catechins-mediated apoptotic effect was also observed in primary APL cells without affecting normal hematopoietic progenitor cells. In the murine xenograft model, Catechins remarkably inhibited tumor growth and induced in situ leukemic cell apoptosis.ConclusionsCatechins might be a potential candidate for APL treatment by activating intrinsic apoptotic pathway and targeting PML-RARα oncoprotein.
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影响因子：
6.7
作者：
Kim, Chang-Yul;Lee, Chan;Jang, Jung-Hee
通讯作者：
Jang, Jung-Hee
影响因子：
11.4
作者：
Gianni, M.;Peviani, M.;Garattini, E.
通讯作者：
Garattini, E.
影响因子：
3.8
作者：
Katiyar, SK;Afaq, F;Mukhtar, H
通讯作者：
Mukhtar, H
影响因子：
2
作者：
Horie, N;Hirabayashi, N;Takeishi, K
通讯作者：
Takeishi, K
全反式视黄酸/三氧化二砷治疗新诊断的急性早幼粒细胞白血病的长期疗效和安全性。
DOI：
10.1073/pnas.0813280106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Hu, Jiong;Liu, Yuan-Fang;Chen, Zhu
通讯作者：
Chen, Zhu