Modulation of mitochondrial functions by the indirect antioxidant sulforaphane: A seemingly contradictory dual role and an integrative hypothesis

Free Radical Biology and Medicine

Volumn 65, Issue , 2013, Pages 1078-1089

  Negrette Guzmán, Mario ^a   Huerta Yepez, Sara ^b   Tapia, Edilia ^c   Pedraza Chaverri, José ^a  

^a UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

^b HOSPITAL INFANTIL DE MÉXICO FEDERICO GÓMEZ   (Mexico)

^c INSTITUTO NACIONAL DE CARDIOLOGÍA IGNACIO CHÁVEZ   (Mexico)

Author keywords

Cancer cells; Cytoprotection; Free radicals; Mitochondria; Mitochondria dependent apoptosis; Mitochondrial biogenesis; Mitochondrial dynamics; Reactive oxygen species; Sulforaphane

Indexed keywords

CASPASE 8; CASPASE 9; CISPLATIN; GENTAMICIN; HEME OXYGENASE 1; HYPOXIA INDUCIBLE FACTOR 1; MITOCHONDRIAL DNA; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; PROTEIN BAX; PROTEIN P53; PYRUVATE DEHYDROGENASE; PYRUVATE DEHYDROGENASE KINASE; REACTIVE OXYGEN METABOLITE; SULFORAPHANE; ANTIOXIDANT; ISOTHIOCYANIC ACID DERIVATIVE; SULFORAFAN;

ANAEROBIC GLYCOLYSIS; ANGIOGENESIS; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; B CELL LYMPHOMA; BIOENERGY; BIOGENESIS; CELL DEATH; CELL PROLIFERATION; CELL PROTECTION; CELL SURVIVAL; COLON ADENOCARCINOMA; DNA FRAGMENTATION; DNA SYNTHESIS; ENZYME ACTIVATION; ENZYME ACTIVITY; GLIOMA; GLUCOSE INTAKE; HUMAN; LEUKEMIA; LIPID PEROXIDATION; MELANOMA CELL; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL PERMEABILITY; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; MYELOMA; NEUROBLASTOMA CELL; NONHUMAN; OXIDATIVE STRESS; OXYGEN CONSUMPTION; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; REVIEW; ANIMAL; DRUG EFFECTS; METABOLISM; NEOPLASM; PHYSIOLOGY;

ANIMALS; ANTIOXIDANTS; APOPTOSIS; HUMANS; ISOTHIOCYANATES; MITOCHONDRIA; MITOCHONDRIAL TURNOVER; NEOPLASMS; OXIDATIVE STRESS;

EID: 84884635067     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2013.08.182     Document Type: Review

References (148)

1. Y. Zhang, P. Talalay, C.G. Cho, and G.H. Posner A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure Proc. Natl. Acad. Sci. USA 89 1992 2399 2403
2. H.R. Vasanthi, S. Mukherjee, and D.K. Das Potential health benefits of broccoli - a chemico-biological overview Mini Rev. Med. Chem 9 2009 749 759
3. A.T. Dinkova-Kostova, and P. Talalay Direct and indirect antioxidant properties of inducers of cytoprotective proteins Mol. Nutr. Food Res. 52 2008 S128 S138
4. L. Gaona-Gaona, E. Molina-Jijón, E. Tapia, C. Zazueta, R. Hernández-Pando, M. Calderón-Oliver, G. Zarco-Márquez, E. Pinzón, and J. Pedraza-Chaverri Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats Toxicology 286 2011 20 27
5. Y. Zhang, and L. Tang Discovery and development of sulforaphane as a cancer chemopreventive phytochemical Acta Pharmacol. Sin. 28 2007 1343 1354 (Pubitemid 47366676)
6. T.W. Kensler, N. Wakabayashi, and S. Biswal Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway Annu. Rev. Pharmacol. Toxicol. 47 2007 89 116
7. M.C. Myzak, and R.H. Dashwood Chemoprotection by sulforaphane: keep one eye beyond Keap1 Cancer Lett. 233 2006 208 218 (Pubitemid 43327375)
8. E.E. Vomhof-Dekrey, and M.J. Picklo Sr. The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism J. Nutr. Biochem. 23 2012 1201 1206
9. A.T. Dinkova-Kostova, W.D. Holtzclaw, R.N. Cole, K. Itoh, N. Wakabayashi, Y. Katoh, M. Yamamoto, and P. Talalay Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants Proc. Natl. Acad. Sci. USA 99 2002 11908 11913 (Pubitemid 34994497)
10. F. Hong, M.L. Freeman, and D.C. Liebler Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane Chem. Res. Toxicol. 18 2005 1917 1926 (Pubitemid 43023050)
11. Y.H. Ahn, Y. Hwang, H. Liu, X.J. Wang, Y. Zhang, K.K. Stephenson, T.N. Boronina, R.N. Cole, A.T. Dinkova-Kostova, P. Talalay, and P.A. Cole Electrophilic tuning of the chemoprotective natural product sulforaphane Proc. Natl. Acad. Sci. USA 107 2010 9590 9595
12. R. Yu, W. Lei, S. Mandlekar, M.J. Weber, C.J. Der, J. Wu, and A.N. Kong Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals J. Biol. Chem. 274 1999 27545 27552
13. J. Jakubíková, J. Sedlák, R. Mithen, and Y. Bao Role of PI3K/Akt and MEK/ERK signaling pathways in sulforaphane- and erucin-induced phase II enzymes and MRP2 transcription G2/M arrest and cell death in Caco-2 cells. Biochem. Pharmacol 69 2005 1543 1552 (Pubitemid 40719490)
14. L. Wang, Y. Chen, P. Sternberg, and J. Cai Essential roles of the PI3 kinase/Akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE Invest. Ophthalmol. Visual Sci. 49 2008 1671 1678
15. A.I. Rojo, P. Rada, J. Egea, A.O. Rosa, M.G. López, and A. Cuadrado Functional interference between glycogen synthase kinase-3 beta and the transcription factor Nrf2 in protection against kainate-induced hippocampal cell death Mol. Cell. Neurosci. 39 2008 125 132
16. Y. Shan, X. Wang, W. Wang, C. He, and Y. Bao p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells Oncol. Rep. 23 2010 1133 1138
17. H.C. Huang, T. Nguyen, and C.B. Pickett Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2 Proc. Natl. Acad. Sci. USA 97 2000 12475 12480
18. M. Salazar, A.I. Rojo, and D. Velasco de Sagarra, R.M.; Cuadrado, A. Glycogen synthase kinase-3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2 J. Biol. Chem. 281 2006 14841 14851 (Pubitemid 43855189)
19. S.K. Niture, A.K. Jain, P.M. Shelton, and A.K. Jaiswal Src subfamily kinases regulate nuclear export and degradation of transcription factor Nrf2 to switch off Nrf2-mediated antioxidant activation of cytoprotective gene expression J. Biol. Chem. 286 2011 28821 28832
20. Y.S. Keum, S. Yu, P.P. Chang, X. Yuan, J.H. Kim, C. Xu, J. Han, A. Agarwal, and A.N. Kong Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells Cancer Res. 66 2006 8804 8813 (Pubitemid 44449198)
21. C.E. Guerrero-Beltrán, P. Mukhopadhyay, B. Horváth, M. Rajesh, E. Tapia, I. García-Torres, J. Pedraza-Chaverri, and P. Pacher Sulforaphane, a natural constituent of broccoli, prevents cell death and inflammation in nephropathy J. Nutr. Biochem. 23 2012 494 500
22. C.T. Yeh, and G.C. Yen Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells Carcinogenesis 26 2005 2138 2148
23. T. Jayakumar, W.F. Chen, W.J. Lu, D.S. Chou, G. Hsiao, C.Y. Hsu, J.R. Sheu, and C.Y. Hsieh A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: ex vivo and in vivo studies J. Nutr. Biochem. 24 2013 1086 1095
24. M. Zamocky, P.G. Furtmüller, and C. Obinger Evolution of catalases from bacteria to humans Antioxid. Redox Signaling 10 2010 1527 15248
25. S.K. Dhar St, and D.K. Clair Manganese superoxide dismutase regulation and cancer Free Radic. Biol. Med. 52 2012 2209 2222
26. H. Zhu, K. Itoh, M. Yamamoto, J.L. Zweier, and Y. Li Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury FEBS Lett 579 2005 3029 3036 (Pubitemid 40797830)
27. L. Gamet-Payrastre, P. Li, S. Lumeau, G. Cassar, M.A. Dupont, S. Chevolleau, N. Gasc, J. Tulliez, and F. Tercé Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells Cancer Res. 60 2000 1426 1433 (Pubitemid 30152017)
28. S.S. Hecht Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism J. Nutr. 129 1999 768 S 774S
29. C.E. Guerrero-Beltrán, M. Calderón-Oliver, J. Pedraza-Chaverri, and Y.I. Chirino Protective effect of sulforaphane against oxidative stress: recent advances Exp. Toxicol. Pathol. 64 2012 503 508
30. S. Orrenius, B. Zhivotovsky, and P. Nicotera Regulation of cell death: the calcium-apoptosis link Nat. Rev. Mol. Cell Biol. 4 2003 552 565 (Pubitemid 36773407)
31. C. Wang, and R.J. Youle The role of mitochondria in apoptosis Annu. Rev. Genet. 43 2009 95 118
32. V. Gogvadze, B. Zhivotovsky, and S. Orrenius The Warburg effect and mitochondrial stability in cancer cells Mol. Aspects Med. 31 2010 60 74
33. A.V. Singh, D. Xiao, K.L. Lew, R. Dhir, and S.V. Singh Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo Carcinogenesis 25 2004 83 90 (Pubitemid 38128621)
34. N.A. Pham, J.W. Jacobberger, A.D. Schimmer, P. Cao, M. Gronda, and D.W. Hedley The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice Mol. Cancer Ther. 3 2004 1239 1248 (Pubitemid 39440169)
35. S.V. Singh, S.K. Srivastava, S. Choi, K.L. Lew, J. Antosiewicz, D. Xiao, Y. Zeng, S.C. Watkins, C.S. Johnson, D.L. Trump, Y.J. Lee, H. Xiao, and A. Herman-Antosiewicz Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species J. Biol. Chem. 280 2005 19911 19924 (Pubitemid 41379520)
36. L. Tang, and Y. Zhang Mitochondria are the primary target in isothiocyanate-induced apoptosis in human bladder cancer cells Mol. Cancer Ther. 4 2008 1250 1259
37. A. Pledgie-Tracy, M.D. Sobolewski, and N.E. Davidson Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines Mol. Cancer Ther. 6 2007 1013 1021 (Pubitemid 46554571)
38. M.J. Chen, W.Y. Tang, C.W. Hsu, Y.T. Tsai, J.F. Wu, C.W. Lin, Y.M. Cheng, and Y.C. Hsu Apoptosis induction in primary human colorectal cancer cell lines and retarded tumor growth in SCID mice by sulforaphane Evid. Based Complement Alternat. Med. 2012 2012 415231
39. S. Orrenius Reactive oxygen species in mitochondria-mediated cell death Drug Metab. Rev. 39 2007 443 455 (Pubitemid 47355728)
40. J. Estaquier, F. Vallette, J.L. Vayssiere, and B. Mignotte The mitochondrial pathways of apoptosis Adv. Exp. Med. Biol. 942 2012 157 183
41. N.D. Marchenko, A. Zaika, and U.M. Moll Death signal-induced localization of p53 protein to mitochondria: a potential role in apoptotic signaling J. Biol. Chem. 275 2000 16202 16212 (Pubitemid 30366932)
42. J.E. Chipuk, T. Kuwana, L. Bouchier-Hayes, N.M. Droin, D.D. Newmeyer, M. Schuler, and D.R. Green Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis Science 303 2004 1010 1014 (Pubitemid 38209704)
43. S. Matoba, J.G. Kang, W.D. Patino, A. Wragg, M. Boehm, O. Gavrilova, P.J. Hurley, F. Bunz, and P.M. Hwang p53 regulates mitochondrial respiration Science 312 2006 1650 1653 (Pubitemid 43902663)
44. C. Fimognari, M. Nüsse, R. Cesari, R. Iori, G. Cantelli-Forti, and P. Hrelia Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane Carcinogenesis 23 2002 581 586 (Pubitemid 34498494)
45. T.P. Hamsa, P. Thejass, and G. Kuttan Induction of apoptosis by sulforaphane in highly metastatic B16F-10 melanoma cells Drug Chem. Toxicol. 34 2011 332 340
46. S. Karmakar, M.S. Weinberg, N.L. Banik, S.J. Patel, and S.K. Ray Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane Neuroscience 141 2006 1265 1280 (Pubitemid 44128679)
47. S. Choi, K.L. Lew, H. Xiao, A. Herman-Antosiewicz, D. Xiao, C.K. Brown, and S.V. Singh D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1 Carcinogenesis 28 2007 151 162 (Pubitemid 44942639)
48. G. Pappa, M. Lichtenberg, R. Iori, J. Barillari, H. Bartsch, and C. Gerhäuser Comparison of growth inhibition profiles and mechanisms of apoptosis induction in human colon cancer cell lines by isothiocyanates and indoles from Brassicaceae Mutat. Res. 599 2006 76 87 (Pubitemid 44041504)
49. E. Rudolf, and M. Cervinka Sulforaphane induces cytotoxicity and lysosome- and mitochondria-dependent cell death in colon cancer cells with deleted p53 Toxicol. In Vitro 25 2011 1302 1309
50. S. Shankar, S. Ganapathy, and R.K. Srivastava Sulforaphane enhances the therapeutic potential of TRAIL in prostate cancer orthotopic model through regulation of apoptosis, metastasis, and angiogenesis Clin. Cancer Res. 14 2008 6855 6866
51. E. Rudolf, H. Andelová, and M. Cervinka Activation of several concurrent proapoptotic pathways by sulforaphane in human colon cancer cells SW620 Food Chem. Toxicol. 47 2009 2366 23673
52. J. Jakubikova, D. Cervi, M. Ooi, K. Kim, S. Nahar, S. Klippel, D. Cholujova, M. Leiba, J.F. Daley, J. Delmore, J. Negri, S. Blotta, D.W. McMillin, T. Hideshima, P.G. Richardson, J. Sedlak, K.C. Anderson, and C.S. Mitsiades Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma Haematologica 96 2011 1170 1179
53. T.Y. Huang, W.C. Chang, M.Y. Wang, Y.R. Yang, and Y.C. Hsu Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway Cell Biochem. Biophys. 63 2012 247 259
54. Y.C. Hsu, S.J. Chang, M.Y. Wang, Y.L. Chen, and T.Y. Huang Growth inhibition and apoptosis of neuroblastoma cells through ROS-independent MEK/ERK activation by sulforaphane Cell. Biochem. Biophys. 66 2013 765 774
55. L. Willems, J. Tamburini, N. Chapuis, C. Lacombe, P. Mayeux, and D. Bouscary PI3K and mTOR signaling pathways in cancer: new data on targeted therapies. Curr Oncol. Rep. 14 2012 129 138
56. L. Chang, and M. Karin Mammalian MAP kinase signalling cascades Nature 410 2001 37 40 (Pubitemid 32225829)
57. D. Xiao, A.A. Powolny, J. Antosiewicz, E.R. Hahm, A. Bommareddy, Y. Zeng, D. Desai, S. Amin, A. Herman-Antosiewicz, and S.V. Singh Cellular responses to cancer chemopreventive agent D,L-sulforaphane in human prostate cancer cells are initiated by mitochondrial reactive oxygen species Pharm. Res. 26 2009 1729 1738
58. N.S. Chandel, and P.T. Schumacker Cells depleted of mitochondrial DNA (rho0) yield insight into physiological mechanisms FEBS Lett. 454 1999 173 176 (Pubitemid 29304594)
59. A. Wiczk, D. Hofman, G. Konopa, and A. Herman-Antosiewicz Sulforaphane, a cruciferous vegetable-derived isothiocyanate, inhibits protein synthesis in human prostate cancer cells Biochim. Biophys. Acta 1823 2012 1295 1305
60. R. Scatena Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation Adv. Exp. Med. Biol. 942 2012 287 308
61. E. Bertl, H. Bartsch, and C. Gerhäuser Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention Mol. Cancer Ther. 5 2006 575 585
62. H. Yao, H. Wang, Z. Zhang, B.H. Jiang, J. Luo, and X. Shi Sulforaphane inhibited expression of hypoxia-inducible factor-1alpha in human tongue squamous cancer cells and prostate cancer cells Int. J. Cancer. 123 2008 1255 1261
63. Y.K. Jeon, D.R. Yoo, Y.H. Jang, S.Y. Jang, and M.J. Nam Sulforaphane induces apoptosis in human hepatic cancer cells through inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4, mediated by hypoxia inducible factor-1-dependent pathway Biochim. Biophys. Acta 1814 2011 1340 1348
64. T. Shibata, A. Kokubu, M. Gotoh, H. Ojima, T. Ohta, M. Yamamoto, and S. Hirohashi Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer Gastroenterology 135 2008 1358 1368
65. P. Zhang, A. Singh, S. Yegnasubramanian, D. Esopi, P. Kombairaju, M. Bodas, H. Wu, S.G. Bova, and S. Biswal Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth Mol. Cancer Ther. 9 2010 336 346
66. J. Dutta, Y. Fan, N. Gupta, G. Fan, and C. Gélinas Current insights into the regulation of programmed cell death by NF-kappaB Oncogene 25 2006 6800 6816 (Pubitemid 44657853)
67. N. Wakabayashi, S.L. Slocum, J.J. Skoko, S. Shin, and T.W. Kensler When NRF2 talks, who's listening? Antioxid Redox Signaling 13 2010 1649 1663
68. Y.S. Keum, T.O. Khor, W. Lin, G. Shen, K.H. Kwon, A. Barve, W. Li, and A.N. Kong Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent kinase pathway Pharm. Res 26 2009 2324 2331
69. P. Kombairaju, J. Ma, R.K. Thimmulappa, S.G. Yan, E. Gabrielson, A. Singh, and S. Biswal Prolonged sulforaphane treatment does not enhance tumorigenesis in oncogenic K-ras and xenograft mouse models of lung cancer J. Carcinog 11 2012 8
70. K. Hu, Y.J. Qi, J. Zhao, H.F. Jiang, X. Chen, and J. Ren Synthesis and biological evaluation of sulforaphane derivatives as potential antitumor agents Eur. J. Med. Chem. 64 2013 529 539
71. M.D. Brand, and D.G. Nicholls Assessing mitochondrial dysfunction in cells Biochem. J. 435 2011 297 312
72. H. Zhu, Z. Jia, J.S. Strobl, M. Ehrich, H.P. Misra, and Y. Li Potent induction of total cellular and mitochondrial antioxidants and phase 2 enzymes by cruciferous sulforaphane in rat aortic smooth muscle cells: cytoprotection against oxidative and electrophilic stress Cardiovasc. Toxicol. 8 2008 115 125
73. C.S. Piao, S. Gao, G.H. Lee, K.i.m. do, S. Park, B.H. Chae, S.W. Chae, and H.J. Kim S.H. Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels Pharmacol. Res. 61 2010 342 348
74. K.D. Garlid, A.D. Costa, C.L. Quinlan, S.V. Pierre, and P. Dos Santos Cardioprotective signaling to mitochondria J. Mol. Cell. Cardiol. 46 2009 858 866
75. J.C. Martinou, and D.R. Green Breaking the mitochondrial barrier Nat. Rev. Mol. Cell Biol. 2 2001 63 67 (Pubitemid 33676963)
76. M. Crompton The mitochondrial permeability transition pore and its role in cell death Biochem. J. 341 1999 233 249 (Pubitemid 29373645)
77. A. Rasola, and P. Bernardi Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis Cell Calcium 50 2011 222 233
78. C.E. Guerrero-Beltrán, M. Calderón-Oliver, E. Martínez-Abundis, E. Tapia, G. Zarco-Márquez, C. Zazueta, and J. Pedraza-Chaverri Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H:quinone oxidoreductase 1 and γ glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LLC-PK1 cells Toxicol. Lett. 199 2010 80 92
79. C.E. Guerrero-Beltrán, M. Calderón-Oliver, E. Tapia, O.N. Medina-Campos, D.J. Sánchez-González, C.M. Martínez- Martínez, K.M. Ortiz-Vega, M. Franco, and J. Pedraza-Chaverri Sulforaphane protects against cisplatin-induced nephrotoxicity Toxicol. Lett. 192 2010 278 285
80. K.W. Kinnally, P.M. Peixoto, S.Y. Ryu, and L.M. Dejean Is mPTP the gatekeeper for necrosis, apoptosis, or both? Biochim. Biophys. Acta 1813 2011 616 622
81. T. Greco, and G. Fiskum Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition J. Bioenerg. Biomembr. 42 2010 491 497
82. T. Greco, J. Shafer, and G. Fiskum Sulforaphane inhibits mitochondrial permeability transition and oxidative stress Free Radic. Biol. Med. 51 2011 2164 21671
83. M.J. Meredith, and D.J. Reed Depletion in vitro of mitochondrial glutathione in rat hepatocytes and enhancement of lipid peroxidation by adriamycin and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) Biochem. Pharmacol. 32 1983 1383 1388 (Pubitemid 13088968)
84. T.E. Gunter, and S.S. Sheu Characteristics and possible functions of mitochondrial Ca(2+) transport mechanisms Biochim. Biophys. Acta 1787 2009 1291 1308
85. D.M. Miller, I.N. Singh, J.A. Wang, and E.D. Hall Administration of the Nrf2-ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo Free Radic. Biol. Med. 57 2013 1 9
86. H. Servais, A. Ortiz, O. Devuyst, S. Denamur, P.M. Tulkens, and M.P. Mingeot-Leclercq Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation Apoptosis 13 2008 11 32
87. M. Negrette-Guzmán, S. Huerta-Yepez, O.N. Medina-Campos, Z.L. Zatarain-Barrón, R. Hernández-Pando, I. Torres, E. Tapia, and J. Pedraza-Chaverri Sulforaphane attenuates gentamicin-induced nephrotoxicity: role of mitochondrial protection. Evid. Based Complement Alternat. Med. 2013 2013 135314
88. V.N. Sumantran Cellular chemosensitivity assays: an overview Methods Mol. Biol. 731 2011 219 236
89. S.D. Chung, T.Y. Lai, C.T. Chien, and H.J. Yu Activating Nrf-2 signaling depresses unilateral ureteral obstruction-evoked mitochondrial stress-related autophagy, apoptosis and pyroptosis in kidney. PLoS One e47299 2012
90. D.K. Priya, R. Gayathri, G.R. Gunassekaran, and D. Sakthisekaran Protective role of sulforaphane against oxidative stress mediated mitochondrial dysfunction induced by benzo(a)pyrene in female Swiss albino mice Pulm. Pharmacol. Ther. 24 2011 110 117
91. P.D. Kalpana Deepa, R. Gayathri, G.R. Gunassekaran, S. Murugan, and D. Sakthisekaran Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis Pharm. Biol. 51 2013 621 628
92. C.A. Piantadosi, M.S. Carraway, A. Babiker, and H.B. Suliman Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1 Circ. Res. 103 2008 1232 1240
93. N.C. MacGarvey, H.B. Suliman, R.R. Bartz, P. Fu, C.M. Withers, K.E. Welty-Wolf, and C.A. Piantadosi Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis Am. J. Respir. Crit. Care Med. 185 2012 851 861
94. R.D. Brose, G. Shin, M.C. McGuinness, T. Schneidereith, S. Purvis, G.X. Dong, J. Keefer, F. Spencer, and K.D. Smith Activation of the stress proteome as a mechanism for small molecule therapeutics Hum. Mol. Genet. 21 2012 4237 4252
95. B.F. Miller, and K.L. Hamilton A perspective on the determination of mitochondrial biogenesis Am. J. Physiol. Endocrinol. Metab. 302 2012 E496 E499
96. M.P. Mattson Dietary factors, hormesis and health Ageing Res. Rev. 7 2008 43 48
97. M.P. Mattson Hormesis defined Ageing Res. Rev. 7 2008 1 7
98. V. Calabrese, C. Cornelius, A.T. Dinkova-Kostova, I. Iavicoli, R. Di Paola, A. Koverech, S. Cuzzocrea, E. Rizzarelli, and E.J. Calabrese Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity Biochim. Biophys. Acta 1822 2012 753 783
99. F. Zanichelli, S. Capasso, M. Cipollaro, E. Pagnotta, M. Cartenì, F. Casale, R. Iori, and U. Galderisi Dose-dependent effects of R-sulforaphane isothiocyanate on the biology of human mesenchymal stem cells: at dietary amounts, it promotes cell proliferation and reduces senescence and apoptosis, while at anti-cancer drug doses, it has a cytotoxic effect Age (Dordrecht) 34 2012 281 293
100. I. Misiewicz, K. Skupińska, E. Kowalska, J. Lubiński, and T. Kasprzycka-Guttman Sulforaphane-mediated induction of a phase 2 detoxifying enzyme NAD(P)H:quinone reductase and apoptosis in human lymphoblastoid cells Acta Biochim. Pol. 51 2004 711 721 (Pubitemid 39296925)
101. W.Y. Choi, B.T. Choi, W.H. Lee, and Y.H. Choi Sulforaphane generates reactive oxygen species leading to mitochondrial perturbation for apoptosis in human leukemia U937 cells Biomed. Pharmacother. 62 2008 637 644
102. W.F. Chu, D.M. Wu, W. Liu, L.J. Wu, D.Z. Li, D.Y. Xu, and X.F. Wang Sulforaphane induces G2-M arrest and apoptosis in high metastasis cell line of salivary gland adenoid cystic carcinoma Oral Oncol. 45 2009 998 1004
103. M. Vermeulen, I.W. Klöpping-Ketelaars, R. van den Berg, and W.H. Vaes Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli J. Agric. Food Chem. 56 2008 10505 10509
104. C.C. Conaway, S.M. Getahun, L.L. Liebes, D.J. Pusateri, D.K. Topham, M. Botero-Omary, and F.L. Chung Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli Nutr. Cancer 38 2000 168 178 (Pubitemid 32762016)
105. J.M. Cramer, and E.H. Jeffery Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men Nutr. Cancer 63 2011 196 201
106. J.D. Clarke, A. Hsu, K. Riedl, D. Bella, S.J. Schwartz, J.F. Stevens, and E. Ho Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design Pharmacol. Res. 64 2011 456 463
107. J.M. Cramer, M. Teran-Garcia, and E.H. Jeffery Enhancing sulforaphane absorption and excretion in healthy men through the combined consumption of fresh broccoli sprouts and a glucoraphanin-rich powder Br. J. Nutr 13 2011 1 6
108. S. Saha, W. Hollands, B. Teucher, P.W. Needs, A. Narbad, C.A. Ortori, D.A. Barrett, J.T. Rossiter, R.F. Mithen, and P.A. Kroon Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compared to fresh broccoli Mol. Nutr. Food Res. 56 2012 1906 1916
109. A.V. Gasper, A. Al-Janobi, J.A. Smith, J.R. Bacon, P. Fortun, C. Atherton, M.A. Taylor, C.J. Hawkey, D.A. Barrett, and R.F. Mithen Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli Am. J. Clin. Nutr. 82 2005 1283 1291 (Pubitemid 43779728)
110. M. Murashima, S. Watanabe, X.G. Zhuo, M. Uehara, and A. Kurashige Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of broccoli sprouts Biofactors 22 2004 271 275 (Pubitemid 40921800)
111. M. Traka, A.V. Gasper, A. Melchini, J.R. Bacon, P.W. Needs, V. Frost, A. Chantry, A.M. Jones, C.A. Ortori, D.A. Barrett, R.Y. Ball, R.D. Mills, and R.F. Mithen Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS One e2568 2008
112. S.L. Navarro, J.L. Chang, S. Peterson, C. Chen, I.B. King, Y. Schwarz, S.S. Li, L. Li, J.D. Potter, and J.W. Lampe Modulation of human serum glutathione S-transferase A1/2 concentration by cruciferous vegetables in a controlled feeding study is influenced by GSTM1 and GSTT1 genotypes Cancer Epidemiol. Biomarkers Prev 18 2009 2974 2978
113. M.A. Riedl, A. Saxon, and D. Diaz-Sanchez Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway Clin. Immunol. 130 2009 244 251
114. T.W. Kensler, J.G. Chen, P.A. Egner, J.W. Fahey, L.P. Jacobson, K.K. Stephenson, L. Ye, J.L. Coady, J.B. Wang, Y. Wu, Y. Sun, Q.N. Zhang, B.C. Zhang, Y.R. Zhu, G.S. Qian, S.G. Carmella, S.S. Hecht, L. Benning, S.J. Gange, J.D. Groopman, and P. Talalay Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China Cancer Epidemiol. Biomarkers Prev. 14 2005 2605 2613 (Pubitemid 41752722)
115. R. Hu, V. Hebbar, B.R. Kim, C. Chen, B. Winnik, B. Buckley, P. Soteropoulos, P. Tolias, R.P. Hart, and A.N. Kong In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat J. Pharmacol. Exp. Ther. 310 2004 263 271 (Pubitemid 38812720)
116. H. Wang, W. Lin, G. Shen, T.O. Khor, A.A. Nomeir, and A.N. Kong Development and validation of an LC-MS-MS method for the simultaneous determination of sulforaphane and its metabolites in rat plasma and its application in pharmacokinetic studies J. Chromatogr. Sci 49 2011 801 806
117. O.L. Veeranki, A. Bhattacharya, J.R. Marshall, and Y. Zhang Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention Br. J. Nutr. 109 2013 25 32
118. Y. Zhang Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells Carcinogenesis 21 2000 1175 1182 (Pubitemid 30389344)
119. Y. Zhang, R.H. Kolm, B. Mannervik, and P. Talalay Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases Biochem. Biophys. Res. Commun. 206 1995 748 755
120. S.D. Cho, G. Li, H. Hu, C. Jiang, K.S. Kang, Y.S. Lee, S.H. Kim, and J. Lu Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells Nutr. Cancer. 52 2005 213 224 (Pubitemid 41579763)
121. J. Wang, and J. Yi Cancer cell killing via ROS: to increase or decrease, that is the question Cancer Biol. Ther. 7 2008 1875 1884
122. B. Halliwell Oxidative stress and cancer: have we moved forward? Biochem J. 401 2007 1 11 (Pubitemid 46115897)
123. E. Panieri, V. Gogvadze, E. Norberg, R. Venkatesh, S. Orrenius, and B. Zhivotovsky Reactive oxygen species generated in different compartments induce cell death, survival, or senescence Free Radic. Biol. Med. 57 2013 176 187
124. B. Westermann Mitochondrial fusion and fission in cell life and death Nat. Rev. Mol. Cell. Biol. 11 2010 872 884
125. V.G. Antico Arciuch, M.E. Elguero, J.J. Poderoso, and M.C. Carreras Mitochondrial regulation of cell cycle and proliferation Antioxid. Redox Signaling 16 2012 1150 1180
126. R.J. Youle, and A.M. van der Bliek Mitochondrial fission, fusion, and stress Science 37 2012 1062 1065
127. S. Montessuit, S.P. Somasekharan, O. Terrones, S. Lucken-Ardjomande, S. Herzig, R. Schwarzenbacher, D.J. Manstein, E. Bossy-Wetzel, G. Basañez, P. Meda, and J.C. Martinou Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization Cell 142 2010 889 901
128. S. Frank, B. Gaume, E.S. Bergmann-Leitner, W.W. Leitner, E.G. Robert, F. Catez, C.L. Smith, and R.J. Youle The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis Dev. Cell 1 2001 515 525 (Pubitemid 33586103)
129. Y.J. Lee, S.Y. Jeong, M. Karbowski, C.L. Smith, and R.J. Youle Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis Mol. Biol. Cell 15 2004 5001 5011 (Pubitemid 39392214)
130. G. Twig, A. Elorza, A.J. Molina, H. Mohamed, J.D. Wikstrom, G. Walzer, L. Stiles, S.E. Haigh, S. Katz, G. Las, J. Alroy, M. Wu, B.F. Py, J. Yuan, J.T. Deeney, B.E. Corkey, and O.S. Shirihai Fission and selective fusion govern mitochondrial segregation and elimination by autophagy EMBO J. 27 2008 433 446 (Pubitemid 351161653)
131. D. Tondera, S. Grandemange, A. Jourdain, M. Karbowski, Y. Mattenberger, S. Herzig, S. Da Cruz, P. Clerc, I. Raschke, C. Merkwirth, S. Ehses, F. Krause, D.C. Chan, C. Alexander, C. Bauer, R. Youle, T. Langer, and J.C. Martinou SLP-2 is required for stress-induced mitochondrial hyperfusion EMBO J. 8 2009 1589 1600
132. S.B. Berman, Y.B. Chen, B. Qi, J.M. McCaffery, E.B. Rucker 3rd, S. Goebbels, K.A. Nave, B.A. Arnold, E.A. Jonas, F.J. Pineda, and J.M. Hardwick Bcl-xL increases mitochondrial fission, fusion, and biomass in neurons J. Cell Biol. 184 2009 707 719
133. H. Li, Y. Chen, A.F. Jones, R.H. Sanger, L.P. Collis, R. Flannery, E.C. McNay, T. Yu, R. Schwarzenbacher, B. Bossy, E. Bossy-Wetzel, M.V. Bennett, M. Pypaert, J.A. Hickman, P.J. Smith, J.M. Hardwick, and E.A. Jonas Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons Proc. Natl. Acad. Sci. USA 105 2008 2169 2174 (Pubitemid 351439483)
134. R. Radpour, A.X. Fan, C. Kohler, W. Holzgreve, and X.Y. Zhong Current understanding of mitochondrial DNA in breast cancer Breast J. 15 2009 505 509
135. L.M. Tseng, P.H. Yin, C.W. Yang, Y.F. Tsai, C.Y. Hsu, C.W. Chi, and H.C. Lee Somatic mutations of the mitochondrial genome in human breast cancers Genes Chromosomes Cancer 50 2011 800 811
136. H. Imanishi, K. Hattori, R. Wada, K. Ishikawa, S. Fukuda, K. Takenaga, K. Nakada, J. Hayashi, and D.N.A. Mitochondrial mutations regulate metastasis of human breast cancer cells. PLoS One e23401 2011
137. M. Kulawiec, K.M. Owens, and K.K. Singh Cancer cell mitochondria confer apoptosis resistance and promote metastasis Cancer Biol. Ther. 8 2009 1378 1385
138. S. Kanematsu, K. Yoshizawa, N. Uehara, H. Miki, T. Sasaki, M. Kuro, Y.C. Lai, A. Kimura, T. Yuri, and A. Tsubura Sulforaphane inhibits the growth of
139. C. Ye, X.O. Shu, L. Pierce, W. Wen, R. Courtney, Y.T. Gao, W. Zheng, and Q. Cai Mutations in the mitochondrial DNA D-loop region and breast cancer risk Breast Cancer Res. Treat. 119 2010 431 436
140. D. Gingras, M. Gendron, D. Boivin, A. Moghrabi, Y. Théorêt, and R. Béliveau Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary anticarcinogen from Brassica vegetables Cancer Lett. 203 2004 35 43 (Pubitemid 37506081)
141. S. Choi, and S.V. Singh Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent Cancer Res 65 2005 2035 2043 (Pubitemid 40478634)
142. J. Jakubikova, Y. Bao, and J. Sedlak Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines Anticancer Res 25 2005 3375 3386 (Pubitemid 41105214)
143. M. Asakage, N.H. Tsuno, J. Kitayama, T. Tsuchiya, S. Yoneyama, J. Yamada, Y. Okaji, S. Kaisaki, T. Osada, K. Takahashi, and H. Nagawa Sulforaphane induces inhibition of human umbilical vein endothelial cells proliferation by apoptosis Angiogenesis 9 2006 83 91 (Pubitemid 44440553)
144. L. Tang, Y. Zhang, H.E. Jobson, J. Li, K.K. Stephenson, K.L. Wade, and J.W. Fahey Potent activation of mitochondria-mediated apoptosis and arrest in S and M phases of cancer cells by a broccoli sprout extract Mol. Cancer Ther. 5 2006 935 944 (Pubitemid 43724593)
145. S.Y. Park, G.Y. Kim, S.J. Bae, Y.H. Yoo, and Y.H. Choi Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3 Oncol. Rep. 18 2007 181 187
146. C.S. Bryant, S. Kumar, S. Chamala, J. Shah, J. Pal, M. Haider, S. Seward, A.M. Qazi, R. Morris, A. Semaan, M.A. Shammas, C. Steffes, R.B. Potti, M. Prasad, D.W. Weaver, and R.B. Batchu Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells Mol. Cancer 9 2010 47
147. S. Kanematsu, N. Uehara, H. Miki, K. Yoshizawa, A. Kawanaka, T. Yuri, and A. Tsubura Autophagy inhibition enhances sulforaphane-induced apoptosis in human breast cancer cells Anticancer Res. 30 2010 3381 3390
148. K. Sakao, and S.V. Singh D,L-Sulforaphane-induced apoptosis in human breast cancer cells is regulated by the adapter protein p66Shc J. Cell. Biochem. 113 2012 599 610