Nickel-induced apoptosis and relevant signal transduction pathways in Caenorhabditis elegans.
ABSTRACT Many investigations have shown that nickel exposure can induce micronuclei generation, inhibit DNA repair and induce cell apoptosis, both in cells and tissues. However, there is a lack of appropriate in vivo animal models to study the underlying mechanisms of nickel-induced apoptosis. The model organism, Caenorhabditis elegans, has been shown to be a good model for investigating many biological processes. In the present study, we detected 0.01 mM nickel induced significantly germline cell apoptosis after treatment for 12 hours, which demonstrated that C. elegans could be a mammalian in vivo substitute model to study the mechanisms of apoptosis. Then gene knockout C. elegans strains were utilized to investigate the relationship between nickel-induced apoptosis and relevant signal pathways, which were involved in DNA damage and repair, apoptosis regulation and damage signal transduction. The results presented here demonstrated that nickel-induced apoptosis was independent of the DNA damage response gene, such as hus-1, p53/cep-1 and egl-1. The loss-of-function of the genes that related to Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPK) signaling cascades suppressed nickel-induced germline apoptosis, while ERK signaling cascades have no effects on the nickel-induced germline apoptosis.
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ABSTRACT: The ability to evade apoptosis is one of the key properties of cancer. The apoptogenic effect of nickel nanowires (Ni NWs) on cancer cell lines has never been adequately addressed. Due to the unique physicochemical characteristics of Ni NWs, we envision the development of a novel anticancer therapeutics specifically for pancreatic cancer. Thus, we investigated whether Ni NWs induce ROS-mediated apoptosis in human pancreatic adenocarcinoma (Panc-1) cells. In this study Ni NWs were fabricated using the electrodeposition method. Synthesized Ni NWs were physically characterized by energy dispersive X-ray analysis, UV-Vis spectroscopy of NanoDrop 2000 (UV-Vis), magnetization study, scanning electron microscopy, and transmission electron microscopy. Assessment of morphological apoptotic characteristics by phase contrast microscopy (PCM), Ni-NWs-induced apoptosis staining with ethidium bromide (EB) and acridine orange (AO) followed by fluorescence microscopy (FM) was performed. For molecular biological and biochemical characterization, Panc-1 cell culture and cytotoxic effect of Ni NWs were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Quantitative apoptosis was analyzed by flow cytometry staining with propidium iodide through cell cycle arrest and generation of ROS using 2', 7'-dichlorofluorescein diacetate fluorescence intensity. In all experiments, Panc-1 cancer cells without any treatment were used as the negative controls. The intracellular uptake of Ni NWs through endocytosis by Panc-1 cells was observed by PCM. EB and AO staining of FM and MTT assay qualitatively and quantitatively confirmed the extent of apoptosis. Flow cytometric cell cycle arrest and ROS generation indicated Ni NWs as inducers of apoptotic cell death. We investigated the role of Ni NWs as inducers of ROS-mediated apoptosis in Panc-1 cells. These results suggested that Ni NWs could be an effective apoptotic agent for Panc-1 cells and have good potential for further research into a clinical treatment selective for pancreatic cancer.International Journal of Nanomedicine 01/2011; 6:1475-85. · 3.46 Impact Factor