Abstract:
: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 (IC50s = 0.4 ± 0.2 for HepG2 and 3.5 ± 0.3 μM 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.
journal_name
Oxid Med Cell Longevjournal_title
Oxidative medicine and cellular longevityauthors
Huang T,Sun Y,Li Y,Wang T,Fu Y,Li C,Li Cdoi
10.1155/2018/4928703subject
Has Abstractpub_date
2018-08-05 00:00:00pages
4928703eissn
1942-0900issn
1942-0994journal_volume
2018pub_type
杂志文章abstract::Acute pancreatitis (AP) is a multifactorial disease characterized by necroinflammatory changes of the pancreas. Our study is the first study which evaluated the relationship between the free radical production, enzymatic and nonenzymatic antioxidants, oxidative damage, and secretory function of the salivary glands of ...
journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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doi:10.1155/2016/2069290
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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