Since caspase-3 activation is a central feature of apoptotic cells, further investigation of the pathways involving CdTe-QD-induced apoptosis was done. Our results showed that CdTe-QDs caused an increase in Fas level and in caspase-8 activity indicating that CdTe-QDs cause apoptosis in HepG2 cells via extrinsic pathways. Our findings align with the previous study by Choi et al. who reported that CdTe-QD treatment to human neuroblastoma cells caused apoptosis associated with increased Fas expression ( Choi et al., 2007). Our results also showed that exposure to CdTe-QDs caused effects on anti-apoptotic protein Bcl2 and pro-apoptotic protein Bax levels, which are biomarkers for the intrinsic pathway ( Dejean

et al., 2006). Bcl2 is a key inhibitor of apoptosis since its over-expression blocks translocation of cytochrome c from mitochondria into cytosol, this website thus preventing cells from undergoing apoptosis ( Yang et al., 1997).

Conversely, over-expression of Bax and its translocation to mitochondria has been shown to promote the release of cytochrome c into cytosol, leading to activation of effector caspases and subsequently to apoptosis ( Finucane et al., 1999). Our results showed CdTe-QDs caused a decrease in Bcl2 and an increase in mitochondrial Bax levels, suggesting intrinsic apoptotic pathway induction. The release of cytochrome c from mitochondria to cytosol confirmed the effects on cellular Bcl2 protein members. In addition, the present study also revealed that CdTe-QDs activated MAPK signaling pathways as indicated Trametinib by increases in phosphorylation levels of JNK and p38. These results are supported by a previous study reporting that activation of JNK and p38 caused phosphorylation and translocation of Bax into mitochondria to cause apoptosis via intrinsic pathway ( Kim et al., 2006). The present study also adds to the findings from the previous studies by Lu et al. (2006) who showed that activation of JNK was required for CdSe-QDs induced apoptosis in human osteoblast cells. Similarly, Chan et al. (2006) reported that CdSe-QDs induced apoptosis in human

neuroblasma cells via intrinsic (mitochondrial) pathway involving JNK activation. However, contrary to the report from Chan and colleagues who showed that their test Tyrosine-protein kinase BLK QDs caused a decrease in Erk level resulting in inhibition of Ras to Erk survival signaling ( Chan et al., 2006), the present study observed an increase in Erk1/2. The reason for the difference between these findings might be due to differences in the test cell lines, as suggested in the existing literature that Cd-induced Erk activation is cell type-dependent ( Martin and Pognonec, 2010). Cadmium has also been shown to cause apoptosis in vitro and in vivo and the apoptosis induced by cadmium is suggested to arise from the effects of ROS generated by the metal ( Hamada et al., 1997 and Oh and Lim, 2006).