腐植酸诱导人早幼粒白血病HL-60细胞凋亡

Humic Acid Induces Apoptosis in Human Premyelocytic Leukemia HL-60 Cells

试验采用人早幼粒白血病HL-60细胞,主要通过细胞活性丧失、染色质凝聚、核小体间DNA断裂等凋亡特征,研究了腐植酸诱导细胞凋亡的效应,观察了不同时间不同剂量(50～400μg/mL)腐植酸对细胞凋亡的影响。腐植酸诱导HL-60细胞凋亡主要与线粒体内细胞色素c的释放有关,并证明伴随着Caspase-3(天冬氨酸特异性半胱氨酸蛋白酶)的激活和PARP[poly(ADP-ribose)polymerase]的特异性蛋白断裂(一种参与凋亡细胞死亡机制的主要成分)。腐植酸诱导细胞凋亡与Bax蛋白水平相关,同时可观察到Bcl-2蛋白水平有微量降低。这些数据分析表明,腐植酸通过诱导细胞凋亡,抑制了HL-60细胞的增殖及生长,这些作用可能具有抗癌性质,对新药产品的开发有潜在帮助。

It has been shown that humic acid,a phenolic polymer,exhibits pro-oxidant and cytotoxic effects.In this study,HA induction of apoptosis was studied using cultured human premyelocytic leukemia HL-60 cells.Treatment at a range of HA concentrations（50～400 μg/mL） resulted in dose-and time-dependent sequences of events marked by apoptosis,as demonstrated through by apoptotic features such as loss of cell viability,chromatin condensation,and internucleosomal DNA fragmentation.This HA-induced apoptosis in the HL-60 cells was mainly associated with the release of cytochromec from the mitochondria.Furthermore,apoptosis in the HL-60 cells was accompanied by the activation of Caspase-3 and the specific proteolytic cleavage of poly（ADP-ribose） polymerase（PARP）,a major component in the apoptotic cell death mechanism.Although the HA-induced apoptosis was associated with Bax protein levels,negligible Bcl-2 reduction was observed.Analysis of the data reported herein reveals that HA exerts antiproliferative action and growth inhibition on HL-60 cells through induction of apoptosis,which may have anticancer properties potentially useful for the development of new drug products.