Growth Inhibition of a Novel Iron Chelator, DpdtC, against Hepatoma Carcinoma Cell Lines Partly Attributed to Ferritinophagy-Mediated Lysosomal ROS Generation

Oxidative Medicine and Cellular Longevity
Tengfei HuangChangzheng Li

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 reveal...Continue Reading

References

Apr 1, 1978·Physiological Reviews·H N Munro, M C Linder
Mar 1, 1989·Archives of Biochemistry and Biophysics·M C LinderG M Nagel
Oct 11, 2002·Free Radical Biology & Medicine·Or Kakhlon, Z Ioav Cabantchik
Apr 12, 2005·Inorganic Chemistry·Natividad GálvezJosé M Domínguez-Vera
Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Megan WhitnallDes R Richardson
Feb 20, 2007·Biochimica Et Biophysica Acta·David A ZeeviGideon Bach
Apr 4, 2007·Chemical Research in Toxicology·Danuta S Kalinowski, Des R Richardson
Nov 10, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Maolin GuoN D Chasteen
May 21, 2008·Annual Review of Nutrition·Martina U MuckenthalerMatthias W Hentze
Nov 11, 2008·Journal of Molecular and Cellular Cardiology·Shigemiki OmiyaKinya Otsu
Aug 13, 2009·Blood·Ivana De DomenicoJerry Kaplan
Nov 10, 2010·Chemical Communications : Chem Comm·Fadi Bou-AbdallahArtem Melman
Nov 26, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Raymond J BergeronShailendra Singh
Mar 30, 2011·Molecular and Cellular Biology·Takeshi AsanoKazuhiro Iwai
Jun 19, 2012·Biochemistry·Kostas PantopoulosL Devireddy
Aug 15, 2012·Journal of Medicinal Chemistry·Raymond J BergeronJames S McManis
Aug 23, 2012·Antioxidants & Redox Signaling·Alexei Terman, Tino Kurz
Jan 9, 2013·Methods in Molecular Biology·Ana Cipak GasparovicNeven Zarkovic
Dec 19, 2013·Nature Chemical Biology·Scott J Dixon, Brent R Stockwell
Feb 8, 2014·Current Opinion in Hematology·Sujit Sheth
Apr 24, 2014·Handbook of Experimental Pharmacology·Wuyang WangHaoxing Xu
May 15, 2015·Biomolecules·Nikolaus Bresgen, Peter M Eckl
Aug 16, 2015·European Journal of Medicinal Chemistry·Xing YanChunhua Qiao
Oct 16, 2015·Molecular Neurobiology·Giorgio BiasiottoIsabella Zanella
Dec 20, 2015·Bioorganic & Medicinal Chemistry Letters·Vincent CorcéDavid Deniaud
Mar 10, 2016·Journal of Molecular Biology·Joseph D Mancias, Alec C Kimmelman
Jul 1, 2016·Nature Communications·Xiaoli ZhangHaoxing Xu
Oct 30, 2016·Free Radical Biology & Medicine·Christiane OttTilman Grune
Dec 8, 2016·Scientific Reports·Mårten FryknäsRolf Larsson
Nov 22, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Zhangyang QiChangzheng Li
Dec 21, 2017·Metallomics : Integrated Biometal Science·A LaM C Linder

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Citations

Jul 20, 2019·Oxidative Medicine and Cellular Longevity·Yanjie SunChangzheng Li
Jul 30, 2019·Oxidative Medicine and Cellular Longevity·Zhuo WangChangzheng Li
May 21, 2020·Nanomedicine·Gregory JonesJonghan Kim
Dec 29, 2018·International Journal of Molecular Sciences·Yafang WangYi Chen
Apr 8, 2020·Oxidative Medicine and Cellular Longevity·Jiankang FengChangzheng Li
Apr 4, 2019·Frontiers in Oncology·Stefania RecalcatiGaetano Cairo
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Zhenyu ZhaiJuxiang Li

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Methods Mentioned

BETA
flow cytometry
Assay
protein assay

Software Mentioned

Syngene G BOX
GraphPad
ImageJ
Prism

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