Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells.
Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells.
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DOI：
10.3892/ijmm_00000366
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发表时间：
2010-03
影响因子：
5.4
通讯作者：
Dou QP
中科院分区：
文献类型：
--
作者：
Davenport A;Frezza M;Shen M;Ge Y;Huo C;Chan TH;Dou QP
化疗仍然是许多类型白血病的主要治疗方法。尽管对延长血液系统恶性肿瘤患者的总生存期有积极影响，但仍需要新的治疗策略来减少非特异性毒性并提高治疗效果。雷公藤红素，来自'雷神藤'和前-表没食子儿茶素没食子酸酯，一个前药物版本的绿色茶多酚表没食子酸酯已显示出强大的生物活性，在体外和体内。这些天然产物是否能增强常规化疗治疗白血病细胞的疗效还有待证实。在这里，我们证明，这些天然产物可以敏化化疗的效果在K-562和Jurkat T人白血病细胞。因此，这种有效的生物活性与白血病细胞杀伤、半胱天冬酶3激活和聚（ADP-核糖）聚合酶切割水平的增加相关。此外，较高水平的凋亡指数与K-562细胞中Bcr-Abl癌蛋白水平的降低有关。综上所述，我们的研究结果提出了一个令人信服的理由，在血液恶性肿瘤的治疗中使用天然产品的组合策略的发展。
Chemotherapy remains the staple of treatment for many types of leukemia. Despite the positive impact on extending overall survival in patients with hematological malignancies, new treatment strategies are needed to reduce the nonspecific toxicity and improve the efficacy of treatment. Celastrol, derived from the ‘Thunder God Vine’ and Pro-EGCG, a pre-drug version of green tea polyphenol EGCG have shown potent biological activity in vitro and in vivo. Whether these natural products augment the efficacy of conventional chemotherapy in the treatment of leukemia cells has yet to be demonstrated. Here we demonstrate that these natural products could sensitize the effect of chemotherapy in both K-562 and Jurkat T human leukemia cells. Accordingly, this potent biological activity was associated with increased levels of leukemia cell killing, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Furthermore, the higher levels of apoptotic indices were associated with decreased levels of Bcr-Abl oncoprotein in K-562 cells. Taken together, our findings present a compelling rationale for the development of combination strategies using natural products in the treatment of hematological malignancies.
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影响因子：
5.1
作者：
Chang, FR;Hayashi, K;Lee, KH
通讯作者：
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Yang, Huanjie;Chen, Di;Dou, Q. Ping
通讯作者：
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