Lihua Ye, Zhe Shi, Huixue Liu
Nov 6, 2012
Citations
1
Influential Citations
13
Citations
Quality indicators
Journal
Biological Trace Element Research
Abstract
Gadolinium (Gd) compounds have important applications as MRI contrast and potential anticancer agents. The present study investigated the mechanisms of the proapoptotic effect of gadolinium chloride (GdCl3) on hepatoblastoma cell line (Hep G2) tumor cells. The experimental results indicated that GdCl3 induced apoptosis of Hep G2 at high concentration and with long time incubation; however, unlike the actions on normal cell lines, GdCl3 did not cause any oxidative stress on tumor cells. Cytochrome c (Cyt c) and apoptosis inducing factor release, Bax translocation, collapse of mitochondria membrane potential, caspase 3 and 8 activation, and Bid cleavage were observed along with a sustained activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2 terminal kinase (JNK). Addition of ERK and JNK inhibitor attenuated the effect of GdCl3 induced apoptosis and Cyt c release. All the results suggested a novel mechanism that GdCl3 induced Hep G2 cell death through intrinsic and external death pathways without significant elevation of reactive oxygen species generation. The present work provided new insight to understand the mechanisms of the biological effects of GdCl3 and implications for the development of anticancer Gd agents.