期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2018, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2018/4928703
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资金
- Natural Science Foundation of China [21571153]
- Henan Science and Technology Agency [152300410118]
- Key Research Project Funding Program of Higher Educational Institutions of Henan Province [19A310021]
- Sanquan College of Xinxiang Medical University
Some iron chelators display significant anticancer activity that may involve ferritin degradation either in proteasomes or in lysosomes, and the latter might involve ferritinophagy with a period. However, the correlation of ferritinophagy with anticancer activity of iron chelator was not fully determined. Revealing the underlying link therefore is required. Di-2-pyridylketone dithiocarbamate (DpdtC), a novel iron chelator, could mobilize iron from ferritin and displayed excellent antitumor against hepatoma carcinoma cell lines (IC(50)s = 0.4 +/- 0.2 for HepG2 and 3.5 +/- 0.3 mu M for Bel-7402, resp.); we speculated that the antiproliferative action of DpdtC might involve ferritinophagy. To this end, the alterations of ferritin, microtubule-associated protein light chain 3 (LC3-II), and nuclear receptor coactivator 4 (NCOA4) were investigated after exposure of DpdtC to the cells. The results revealed that DpdtC could cause increases of autophagic vacuoles and LC3-II. The data from cellular immunofluorescence and Western blotting showed a reciprocal relation between abundances of ferritin and LC3-II, but the trends of NCOA4 and LC3-II in abundance were in a similar manner, indicating that a ferritinophagy occurred. Further studies revealed that the ferritinophagy evoked an iron-driven intralysosomal oxidative reaction, resulting in LMP change and lipid peroxidation. Thus, a ferritinophagy-mediated lysosomal ROS generation playing a role in the antiproliferative action of DpdtC could be proposed, which will enrich our knowledge of iron chelator in cancer therapy.
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