A reactivity-based probe of the intracellular labile ferrous iron pool

Nature Chemical Biology

Volumn 12, Issue 9, 2016, Pages 680-685

  Spangler, Benjamin ^a   Morgan, Charles W ^a   Fontaine, Shaun D ^a   Wal, Mark N Vander ^b   Chang, Christopher J ^b   Wells, James A ^a,c   Renslo, Adam R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FERROPORTIN; FERROUS ION; HEPCIDIN; PUROMYCIN; FLUORESCENT DYE; SPIRO COMPOUND;

ACCURACY; ARTICLE; CANCER CELL; CONTROLLED STUDY; DRUG RELEASE; DRUG SCREENING; DRUG SENSITIVITY; EXTRACELLULAR MATRIX; FENTON REACTION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE TEST; IN VITRO STUDY; INTRACELLULAR SPACE; IRON STORAGE; IRON TRANSPORT; MOLECULAR PROBE; OSTEOSARCOMA CELL LINE; OXIDATION REDUCTION STATE; PRIORITY JOURNAL; PROTEIN PROCESSING; CHEMICAL STRUCTURE; CHEMISTRY; FLUORESCENT ANTIBODY TECHNIQUE; METABOLISM; SYNTHESIS;

FERROUS COMPOUNDS; FLUORESCENT ANTIBODY TECHNIQUE; FLUORESCENT DYES; HUMANS; MOLECULAR STRUCTURE; PUROMYCIN; SPIRO COMPOUNDS;

EID: 84976892410     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.2116     Document Type: Article

References (45)

1. Torti, S.V. & Torti, F.M. Iron and cancer: more ore to be mined. Nat. Rev. Cancer 13, 342-355 (2013).
2. Bandyopadhyay, S., Chandramouli, K.K. & Johnson, M.K. Iron-sulphur cluster biosynthesis. Biochem. Soc. Trans. 36, 1112-1119 (2008).
3. Johnson, D.C., Dean, D.R., Smith, A.D. & Johnson, M.K. Structure, function, and formation of biological iron-sulfur clusters. Annu. Rev. Biochem. 74, 247-281 (2005).
4. Kurz, T., Eaton, J.W. & Brunk, U.T. The role of lysosomes in iron metabolism and recycling. Int. J. Biochem. Cell Biol. 43, 1686-1697 (2011).
5. ONeill, P.M. & Posner, G.H. A medicinal chemistry perspective on artemisinin and related endoperoxides. J. Med. Chem. 47, 2945-2964 (2004).
6. Mercer, A.E. et al. Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J. Biol. Chem. 282, 9372-9382 (2007).
7. Dixon, S.J. & Stockwell, B.R. The role of iron and reactive oxygen species in cell death. Nat. Chem. Biol. 10, 9-17 (2014).
8. Pantopoulos, K. Iron metabolism and the IRE/IRP regulatory system: An update. Ann. NY Acad. Sci. 1012, 1-13 (2004).
9. Wang, J. & Pantopoulos, K. Regulation of cellular iron metabolism. Biochem. J. 434, 365-381 (2011).
10. Richardson, D.R. & Ponka, P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim. Biophys. Acta 1331, 1-40 (1997).
11. Fernaeus, S. & Land, T. Increased iron-induced oxidative stress and toxicity in scrapie-infected neuroblastoma cells. Neurosci. Lett. 382, 217-220 (2005).
12. Wessling-Resnick, M. Iron homeostasis and the inflammatory response. Annu. Rev. Nutr. 30, 105-122 (2010).
13. Boult, J. et al. Overexpression of cellular iron import proteins is associated with malignant progression of esophageal adenocarcinoma. Clin. Cancer Res. 14, 379-387 (2008).
14. Kakhlon, O., Gruenbaum, Y. & Cabantchik, Z.I. Ferritin expression modulates cell cycle dynamics and cell responsiveness to H-ras-induced growth via expansion of the labile iron pool. Biochem. J. 363, 431-436 (2002).
15. Pinnix, Z.K. et al. Ferroportin and iron regulation in breast cancer progression and prognosis. Sci. Transl. Med. 2, 43ra56 (2010).
16. Wu, K.J., Polack, A. & Dalla-Favera, R. Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283, 676-679 (1999).
17. Toyokuni, S. Role of iron in carcinogenesis: cancer as a ferrotoxic disease. Cancer Sci. 100, 9-16 (2009).
18. Miller, L.D. et al. An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res. 71, 6728-6737 (2011).
19. Kakhlon, O. & Cabantchik, Z.I. The labile iron pool: Characterization, measurement, and participation in cellular processes. Free Radic. Biol. Med. 33, 1037-1046 (2002).
20. Epsztejn, S. et al. Fluorescence analysis of the labile iron pool of mammalian cells. Anal. Biochem. 248, 31-40 (1997).
21. Petrat, F., de Groot, H., Sustmann, R. & Rauen, U. The chelatable iron pool in living cells: A methodically defined quantity. Biol. Chem. 383, 489-502 (2002).
22. Hirayama, T., Okuda, K. & Nagasawa, H. A highly selective turn-on fluorescent probe for iron(ii) to visualize labile iron in living cells. Chem. Sci. 4, 1250-1256 (2013).
23. Au-Yeung, H.Y., Chan, J., Chantarojsiri, T. & Chang, C.J. Molecular imaging of labile iron(ii) pools in living cells with a turn-on fluorescent probe. J. Am. Chem. Soc. 135, 15165-15173 (2013).
24. Aron, A.T., Ramos-Torres, K.M., Cotruvo, J.A. & Chang, C.J. Recognition-And reactivity-based fluorescent probes for studying transition metal signaling in living systems. Acc. Chem. Res. 48, 2434-2442 (2015).
25. Valecha, N. et al. Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium falciparum malaria: A phase ii, multicenter, randomized, dose-finding clinical trial. Clin. Infect. Dis. 51, 684-691 (2010).
26. Borstnik, K., Paik, I., Shapiro, T.A. & Posner, G.H. Antimalarial chemotherapeutic peroxides: Artemisinin, yingzhaosu A and related compounds. Int. J. Parasitol. 32, 1661-1667 (2002).
27. Valecha, N. et al. Arterolane maleate plus piperaquine phosphate for treatment of uncomplicated plasmodium falciparum malaria: A comparative, multicenter, randomized clinical trial. Clin. Infect. Dis. 55, 663-671 (2012).
28. Charman, S.A. et al. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proc. Natl. Acad. Sci. USA 108, 4400-4405 (2011).
29. Creek, D.J. et al. Relationship between antimalarial activity and heme alkylation for spiro-And dispiro-1, 2, 4-Trioxolane antimalarials. Antimicrob. Agents Chemother. 52, 1291-1296 (2008).
30. Creek, D.J. et al. Iron-mediated degradation kinetics of substituted dispiro-1, 2, 4-Trioxolane antimalarials. J. Pharm. Sci. 96, 2945-2956 (2007).
31. Tang, Y. et al. Dispiro-1, 2, 4-Trioxane analogues of a prototype dispiro-1, 2, 4-Trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(ii). J. Org. Chem. 70, 5103-5110 (2005).
32. Wang, X. et al. Spiroadamantyl 1, 2, 4-Trioxolane, 1, 2, 4-Trioxane, and 1, 2, 4-Trioxepane pairs: relationship between peroxide bond iron(ii) reactivity, heme alkylation efficiency, and antimalarial activity. Bioorg. Med. Chem. Lett. 19, 4542-4545 (2009).
33. Mahajan, S.S. et al. A fragmenting hybrid approach for targeted delivery of multiple therapeutic agents to the malaria parasite. ChemMedChem 6, 415-419 (2011).
34. Fontaine, S.D., Dipasquale, A.G. & Renslo, A.R. Efficient and stereocontrolled synthesis of 1, 2, 4-Trioxolanes useful for ferrous iron-dependent drug delivery. Org. Lett. 16, 5776-5779 (2014).
35. Fontaine, S.D. et al. Drug delivery to the malaria parasite using an arterolane-like scaffold. ChemMedChem 10, 47-51 (2015).
36. Petrat, F., Rauen, U. & de Groot, H. Determination of the chelatable iron pool of isolated rat hepatocytes by digital fluorescence microscopy using the fluorescent probe, phen green SK. Hepatology 29, 1171-1179 (1999).
37. Chen, C. & Paw, B.H. Cellular and mitochondrial iron homeostasis in vertebrates. Biochim. Biophys. Acta 1823, 1459-1467 (2012).
38. Yan, C.Y., Ferrari, G. & Greene, L.A. N-Acetylcysteine-promoted survival of PC12 cells is glutathione-independent but transcription-dependent. J. Biol. Chem. 270, 26827-26832 (1995).
39. Mukherjee, T.K., Mishra, A.K., Mukhopadhyay, S. & Hoidal, J.R. High concentration of antioxidants N-Acetylcysteine and mitoquinone-Q induces intercellular adhesion molecule 1 and oxidative stress by increasing intracellular glutathione. J. Immunol. 178, 1835-1844 (2007).
40. Frikke-Schmidt, H. & Lykkesfeldt, J. Keeping the intracellular vitamin C at a physiologically relevant level in endothelial cell culture. Anal. Biochem. 397, 135-137 (2010).
41. Gao, J.P., Friedman, S. & Lanks, K.W. The role of reduced nicotinamide adenine dinucleotide phosphate in glucose dependent and temperature dependent doxorubicin cytotoxicity. Cancer Chemother. Pharmacol. 33, 191-196 (1993).
42. Ishii, T., Sugita, Y. & Bannai, S. Regulation of glutathione levels in mouse spleen lymphocytes by transport of cysteine. J. Cell. Physiol. 133, 330-336 (1987).
43. Kang, Y.J., Feng, Y.I. & Hatcher, E.L. Glutathione stimulates A549 cell proliferation in glutamine-deficient culture: The effect of glutamate supplementation. J. Cell. Physiol. 161, 589-596 (1994).
44. Espósito, B.P., Epsztejn, S., Breuer, W. & Cabantchik, Z.I. A review of fluorescence methods for assessing labile iron in cells and biological fluids. Anal. Biochem. 304, 1-18 (2002).
45. Martins, M.M. et al. Linking tumor mutations to drug responses via a quantitative chemical-genetic interaction map. Cancer Discov. 5, 154-167 (2015).