利用中药治疗癌症并不是什么新闻,著名的砒霜就是治疗白血病的一种有效中药,近年来不少研究组展开了利用天然中草药治疗癌症的研究,近期来自中国药科大学,天然药物活性组分与药效国家重点实验室等处的研究人员就发现了一种古老的中药:黄芩的主要成分能通过作用于一种关键酶,影响AML癌细胞的增殖,并指出这一成分也许能用于AML癌症治疗。相关研究成果公布在3月《血液》(Blood)杂志上。
领导这一研究的是中国药科大学郭青龙教授,郭青龙教授主要从事肿瘤的发病机制及抗肿瘤药的发现性研究,近几年发表研究论文100余篇,SCI收载80余篇,总引用次数达到600余次,此前曾在脑胶质瘤发病机制研究方面获得新的发现。
汉黄芩苷(Wogonoside)是从中药黄芩(Scutellaria baicalensis Georgi)中提取的主要黄酮类成分,黄芩是一种古老的中草药,李时珍在《本草纲目》中曾自述说,他20岁那年,因患感冒咳嗽,骨蒸发热,肌肤如火燎一样热,尽管用了柴胡、麦冬等药都不见好,他父亲单用黄芩一两煎汤,让李时珍服下,很快病情就得到了好转。因此黄芩被认为具有清热燥湿等功效。
在这项研究中,研究人员分析了汉黄芩苷对急性髓系白血病(AML)的治疗作用,他们针对AML细胞系和来自患者的AML细胞展开了研究,发现汉黄芩苷在体外和体内都表现出了抗细胞增殖的特性。而且这种成分能通过诱导G1期阻滞和促进分化,有效抑制U937和HL-60细胞的增殖。
此外这项研究还表明,汉黄芩苷能显着增加磷脂爬行酶1(phospholipid scramblase 1,PLSCR1)的转录,这是由汉黄芩苷对细胞周期和分化相关基因的影响而导致的,这些影响包括促进p21cip的表达,以及抑制c-Myc基因的表达。
汉黄芩苷也能促进PLSCR1进入细胞核,结合到1,4,5-三磷酸肌醇受体1(IP3R1)的启动子上,从而增加了IP3R1的表达。并且研究人员还通过RNA干扰抑制PLSCR1的表达,发现这能部分阻断汉黄芩苷诱导细胞周期阻滞和分化,扰乱汉黄芩苷相关的分子事件。
因此,研究人员认为这项研究结果表明,汉黄芩苷可以作为AML治疗中的一种候选药物。
近期瑞金医院的陈竺陈赛娟院士研究组也发现了一种萜类化合物:毛萼乙素(Eriocalyxin B,EriB)能通过靶向关键信号通路,选择性调控Th1和Th17细胞,发挥强有力的抗炎作用,这不仅有助于癌症治疗的研发,也为自身免疫疾病的治疗,也提出了一种独特的治疗方向。(生物谷Bioon.com)
doi:10.1182/blood-2012-11-466219
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Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells
Yan Chen, Hui Hui, Hao Yang, Kai Zhao, Yansu Qin, Cong Gu, Xiaotang Wang
Wogonoside is the main flavonoid component derived from the root of Scutellaria baicalensis Georgi. It is a popular Chinese herbal medicine with the potential to treat hematologic malignancies. In this study, we investigated the anti-cancer effects of wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted anti-proliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through induction of G1 phase arrest and promotion of differentiation. We also demonstrated that wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle- and differentiation-related genes, including up-regulation of p21cip and down-regulation of c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked wogonoside-induced cell cycle arrest and differentiation and disturbed the wogonoside-associated molecular events. The results of this study therefore suggest that wogonoside may represent a therapeutic candidate for the treatment of AML.