AKT/NF-κB inhibitor xanthohumol targets cell growth and angiogenesis in hematologic malignancies
AKT/NF-κB inhibitor xanthohumol targets cell growth and angiogenesis in hematologic malignancies
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DOI：
10.1002/cncr.23017
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发表时间：
2007-11-01
期刊：
影响因子：
6.2
通讯作者：
Ferrari, Nicoletta
中科院分区：
文献类型：
--
作者：
Dell'Eva, Raffaella;Ambrosini, Claudia;Ferrari, Nicoletta
背景白血病依赖于Akt/NF-kB激活和血管生成。抗血管生成Akt/NF-kB抑制剂黄腐酚（XN）对急性和慢性髓性白血病细胞系（AML，CML）和来自患者的新鲜样品具有体外活性。细胞增殖的抑制与细胞凋亡的诱导和VEGF分泌的减少有关。在XN存在下观察到的细胞侵袭、金属蛋白酶产生和与内皮细胞的粘附减少可以预防体内危及生命的白细胞停滞和组织浸润并发症。由于内皮细胞和造血细胞在其发育和生长中相互关联，因此用具有细胞毒性和抗血管生成活性的药物靶向肿瘤细胞和内皮细胞可能导致协同抗肿瘤作用，从而中断白血病和内皮细胞之间的相互刺激循环。
BACKGROUND. Leukemias are dependent on Akt/NF-kB activation and angiogenesis.METHODS. The antiangiogenic Akt/NF-kB inhibitor xanthohumol (XN) has in vitro activity against acute and chronic myelogenous leukemia cell lines (AML, CML) and fresh samples from patients were investigated.RESULTS. Inhibition of cell proliferation is associated with induction of apoptosis and reduced VEGF secretion. Decreased cell invasion, metalloprotease production, and adhesion to endothelial cells observed in the presence of XN could prevent in vivo life-threatening complications of leukostasis and tissue infiltration.CONCLUSIONS. As endothelial cells and hematopoietic cells are mutually correlated in their development and growth, targeting both tumor cells and endothelial cells with agents possessing cytotoxic and antiangiogenic activities may lead to synergistic antitumor effects interrupting a reciprocal stimulatory loop between leukemia and endothelial cells.