Securinine, a myeloid differentiation agent with therapeutic potential for AML.
Securinine, a myeloid differentiation agent with therapeutic potential for AML.
复制标题
DOI：
10.1371/journal.pone.0021203
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wald DN
中科院分区：
文献类型：
--
作者：
Gupta K;Chakrabarti A;Rana S;Ramdeo R;Roth BL;Agarwal ML;Tse W;Agarwal MK;Wald DN
由于急性髓系白血病(AML)的特征是成熟停滞，因此诱导白血病细胞成熟是非常可取的治疗策略。这种治疗策略有可能避免传统的急性髓细胞白血病疗法所产生的显著副作用。我们鉴定了一种天然化合物一叶卡宾，作为一种白血病分化诱导剂。一叶珊瑚碱是一种从植物中提取的生物碱，以前曾被临床用于治疗主要与神经相关的疾病。一叶绿碱可诱导多种髓系白血病细胞系以及原发白血病患者样本的单核细胞分化。一叶绿碱治疗AML的临床潜力可以从它在细胞系和患者样本中诱导显著生长停滞的能力以及在显著损害AML裸鼠肿瘤生长的活性中看出。此外，一叶珊瑚碱可以与目前使用的药物如全反式维甲酸和地西他滨协同诱导分化。本研究揭示了一叶菜碱通过激活DNA损伤信号诱导分化。一叶绿碱是一种很有前途的新的单核细胞分化诱导剂，已在临床上用于非相关性疾病。
As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potential of avoiding the significant side effects that occur with the traditional AML therapeutics. We identified a natural compound securinine, as a leukemia differentiation-inducing agent. Securinine is a plant-derived alkaloid that has previously been used clinically as a therapeutic for primarily neurological related diseases. Securinine induces monocytic differentiation of a wide range of myeloid leukemia cell lines as well as primary leukemic patient samples. Securinine's clinical potential for AML can be seen from its ability to induce significant growth arrest in cell lines and patient samples as well as its activity in significantly impairing the growth of AML tumors in nude mice. In addition, securinine can synergize with currently employed agents such as ATRA and decitabine to induce differentiation. This study has revealed securinine induces differentiation through the activation of DNA damage signaling. Securinine is a promising new monocytic differentiation inducing agent for AML that has seen previous clinical use for non-related disorders.
登录
查看更多内容
影响因子：
6.4
作者：
COLLINS, SJ;BODNER, A;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
11.4
作者：
Asada, M;Yamada, T;Mizutani, S
通讯作者：
Mizutani, S
影响因子：
3.7
作者：
Meyer M;Rübsamen D;Slany R;Illmer T;Stabla K;Roth P;Stiewe T;Eilers M;Neubauer A
通讯作者：
Neubauer A
影响因子：
11.2
作者：
Wald, David N.;Vermaat, Hanna M.;Tse, William
通讯作者：
Tse, William
影响因子：
4.8
作者：
Rana, Sonia;Gupta, Kalpana;Wald, David N.
通讯作者：
Wald, David N.