Mak Duncan H, Schober Wendy D, Chen Wenjing, Heller Jonathan, Andreeff Michael, Carter Bing Z
Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Leuk Lymphoma. 2007 Apr;48(4):774-85. doi: 10.1080/10428190601186143.
Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest and suppress human xenograft tumor growth by inhibiting Cdc2 and survivin. We examined the effect of M4N on leukemia and found that M4N inhibited growth and induced cell death in leukemic cell lines and blasts from AML patients. However, no significant changes in Cdc2 and survivin levels and G2 arrest were observed. Cell death and growth inhibition were dependent neither on XIAP, Bcl-2, and Bcl-X(L) levels nor on caspase-8. M4N did not promote cell differentiation in HL-60 cells. Interestingly, significant inhibition of AKT phosphorylation was observed in M4N treated OCI-AML3 cells. Collectively, our data showed that M4N inhibited cell growth and induced cell death in both leukemic cell lines and AML patient sample via a mechanism not mediated by Cdc2 and survivin inhibition and suggested that the extrinsic and the mitochondrial apoptotic pathways are not essential.
四 - O - 甲基去甲二氢愈创木酸（M4N）已被证明可通过抑制Cdc2和生存素诱导G2期阻滞并抑制人异种移植肿瘤的生长。我们研究了M4N对白血病的影响，发现M4N可抑制白血病细胞系以及急性髓系白血病（AML）患者原始细胞的生长并诱导细胞死亡。然而，未观察到Cdc2和生存素水平以及G2期阻滞有显著变化。细胞死亡和生长抑制既不依赖于X连锁凋亡抑制蛋白（XIAP）、B细胞淋巴瘤/白血病 - 2（Bcl - 2）和Bcl - X（L）水平，也不依赖于半胱天冬酶 - 8（caspase - 8）。M4N不会促进HL - 60细胞的分化。有趣的是，在经M4N处理的OCI - AML3细胞中观察到AKT磷酸化受到显著抑制。总体而言，我们的数据表明，M4N通过一种不依赖于抑制Cdc2和生存素的机制抑制白血病细胞系和AML患者样本中的细胞生长并诱导细胞死亡，这表明外在凋亡途径和线粒体凋亡途径并非必不可少。
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