Article

ROS-mediated autophagy was involved in cancer cell death induced by novel copper(II) complex

School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie (Impact Factor: 2.01). 09/2009; 62(5):577-82. DOI: 10.1016/j.etp.2009.08.001
Source: PubMed

ABSTRACT In this study, we investigated autophagy induced in HeLa cells by copper(II) complex of ethyl 2-[bis(2-pyridylmethyl)amino] propionate ligand (ETDPA) (formula: [(ETDPA)Cu(phen)](ClO4)2 (abbreviated as LCu),a novel synthetic copper(II) complex whose DNA binding activity has been proved. Cell viability, autophagic levels and generation of ROS were evaluated following the exposure to LCu. LCu-induced cell death in a dose- and time-dependent manner, which was demonstrated by enhanced fluorescence intensity of monodansylcadervarine (MDC), as well as elevated expression of autophagy-related protein MAP-LC3. These phenomena were all attenuated after pretreatment with autophagy inhibitors 3-MA or NH(4)Cl. Furthermore, our data indicated that LCu-triggered autophagy through ROS: cellular ROS levels were increased after LCu treatment, which was reversed by ROS scavenger NAC (N-acetylcysteine). As a consequence, Lcu-mediated autophagy was partly blocked by NAC. In summary, we synthesized a novel copper(II) complex and showed that this compound was effective in killing HeLa cells via ROS-triggered autophagic pathway.

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    • "These results suggest that different apoptosis pathways may be activated by Cu exposure, also suggesting the existence of crosstalk interactions between them. A schematic representation of hypothetical Cu apoptosis pathways activation, based on the present results and the current knowledge, is presented in Fig. 4. The Cu toxicity is attributed, at least in part, to its ability to induce ROS formation (Bopp et al., 2008; Sandrini et al., 2009; Guo et al., 2010) which, in turn, has previously been associated with the activation of p53 (Li et al., 1998; Ostrakhovitch and Cherian, 2005; Tassabehji et al., 2005). In fact, the early increase in mRNA expression of p53 gene, observed in the present study, is suggestive of its involvement in apoptosis activation, since TUNEL-positive cells became more evident soon after 6 h of Cu exposure (Fig. 4-Box 1). "
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