Khamaisie Hazem, Sussan Sherbel, Tal Michael, Najajreh Yousef, Ruthardt Martin, Mahajna Jamal
Cancer Drug Discovery Program, Migal, Kiryat Shmona, 11016, Israel.
Anticancer Res. 2011 Jan;31(1):177-83.
The hallmark of chronic myeloid leukemia (CML) is the abnormal activity of p210(Bcr-Abl) kinase. Selective kinase inhibitors such as imatinib or nilotinib have been established successfully for the treatment of CML. Despite high rates of clinical response, CML patients can develop resistance to these kinase inhibitors mainly due to point mutations within the Abl kinase domain of the fusion protein. Previously, we reported that a crude extract of the mushroom Daedalea gibbosa inhibited kinase activity of Bcr-Abl kinase. Here we report on the identification of the active component of Daedalea gibbosa, oleic acid, which inhibited Bcr-Abl kinase autophosphorylation in Ba/F3 cells and exhibited anti-CML activity in a BCR/ABL-positive mouse model.
慢性髓性白血病(CML)的标志是p210(Bcr-Abl)激酶的异常活性。选择性激酶抑制剂如伊马替尼或尼罗替尼已成功用于治疗CML。尽管临床缓解率很高,但CML患者可能会对这些激酶抑制剂产生耐药性,主要原因是融合蛋白的Abl激酶结构域内的点突变。此前,我们报道过蘑菇大秃马勃的粗提物可抑制Bcr-Abl激酶的活性。在此我们报告大秃马勃活性成分油酸的鉴定,该成分可抑制Ba/F3细胞中Bcr-Abl激酶的自磷酸化,并在BCR/ABL阳性小鼠模型中表现出抗CML活性。