Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

The Tangled Mitochondrial Metabolism in Cancer: An Innovative Pharmacological Approach

Author(s): Patrizia Bottoni and Roberto Scatena*

Volume 27, Issue 13, 2020

Page: [2106 - 2117] Pages: 12

DOI: 10.2174/0929867326666190823163009

Price: $65

Abstract

Background: Mitochondria are remarkably gaining significant and different pathogenic roles in cancer (i.e., to sustain specific metabolism, to activate signaling pathways, to promote apoptosis resistance, to favor cancer cell dissemination, and finally to facilitate genome instability). Interestingly, all these roles seem to be linked to the fundamental activity of mitochondria, i.e. oxidative metabolism. Intriguingly, a typical modification of mitochondrial oxidative metabolism and reactive oxygen species production/ neutralization seems to have a central role in all these tangled pathogenic roles in cancer. On these bases, a careful understanding of the molecular relationships between cancer and mitochondria may represent a fundamental step to realize therapeutic approaches blocking the typical cancer progression.

The main aim of this review is to stress some neglected aspects of oxidative mitochondrial metabolism of cancer cells to promote more translational research with diagnostic and therapeutic potential.

Methods: We reviewed the available literature regarding clinical and experimental studies on various roles of mitochondria in cancer, with attention to the cancer cell mitochondrial metabolism.

Results: Mitochondria are an important source of reactive oxygen species. Their toxic effects seem to increase in cancer cells. However, it is not clear if damage depends on ROS overproduction and/or defect in detoxification. Failure of both these processes is likely a critical component of the cancer process and is strictly related to the actual microenvironment of cancer cells.

Conclusions: Mitochondria, also by ROS production, have a fundamental pathogenetic role in promoting and maintaining cancer and its spreading. To carefully understand the tangled redox state of cancer cells mitochondria represents a fundamental step to realize therapeutic approaches blocking the typical cancer progression.

Keywords: Molecular therapeutics, mitochondria, ROS, cancer, metabolism, antioxidants, oxidative stress, diagnostic biomarkers.

« Previous Next »
[1]
Ishikawa, K.; Takenaga, K.; Akimoto, M.; Koshikawa, N.; Yamaguchi, A.; Imanishi, H.; Nakada, K.; Honma, Y.; Hayashi, J. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science, 2008, 320(5876), 661-664.
[http://dx.doi.org/10.1126/science.1156906] [PMID: 18388260]
[2]
Zielonka, J.; Kalyanaraman, B. “ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis”--a critical commentary. Free Radic. Biol. Med., 2008, 45(9), 1217-1219.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.07.025] [PMID: 18789385]
[3]
Xia, C.; Meng, Q.; Liu, L.Z.; Rojanasakul, Y.; Wang, X.R.; Jiang, B.H. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res., 2007, 67(22), 10823-10830.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0783] [PMID: 18006827]
[4]
Sharma, L.K.; Fang, H.; Liu, J.; Vartak, R.; Deng, J.; Bai, Y. Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation. Hum. Mol. Genet., 2011, 20(23), 4605-4616.
[http://dx.doi.org/10.1093/hmg/ddr395] [PMID: 21890492]
[5]
Goto, M.; Miwa, H.; Suganuma, K.; Tsunekawa-Imai, N.; Shikami, M.; Mizutani, M.; Mizuno, S.; Hanamura, I.; Nitta, M. Adaptation of leukemia cells to hypoxic condition through switching the energy metabolism or avoiding the oxidative stress. BMC Cancer, 2014, 14, 76.
[http://dx.doi.org/10.1186/1471-2407-14-76] [PMID: 24506813]
[6]
Darash-Yahana, M.; Pozniak, Y.; Lu, M.; Sohn, Y.S.; Karmi, O.; Tamir, S.; Bai, F.; Song, L.; Jennings, P.A.; Pikarsky, E.; Geiger, T.; Onuchic, J.N.; Mittler, R.; Nechushtai, R. Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters. Proc. Natl. Acad. Sci. USA, 2016, 113(39), 10890-10895.
[http://dx.doi.org/10.1073/pnas.1612736113] [PMID: 27621439]
[7]
Weinberg, F.; Hamanaka, R.; Wheaton, W.W.; Weinberg, S.; Joseph, J.; Lopez, M.; Kalyanaraman, B.; Mutlu, G.M.; Budinger, G.R.; Chandel, N.S. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl. Acad. Sci. USA, 2010, 107(19), 8788-8793.
[http://dx.doi.org/10.1073/pnas.1003428107] [PMID: 20421486]
[8]
Hole, P.S.; Pearn, L.; Tonks, A.J.; James, P.E.; Burnett, A.K.; Darley, R.L.; Tonks, A. Ras-induced reactive oxygen species promote growth factor-independent proliferation in human CD34+ hematopoietic progenitor cells. Blood, 2010, 115(6), 1238-1246.
[http://dx.doi.org/10.1182/blood-2009-06-222869] [PMID: 20007804]
[9]
Stefano, G.B.; Kream, R.M. Cancer: Mitochondrial Origins. Med. Sci. Monit., 2015, 21, 3736-3739.
[http://dx.doi.org/10.12659/MSM.895990] [PMID: 26621573]
[10]
Sabharwal, S.S.; Schumacker, P.T. Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles’ heel? Nat. Rev. Cancer, 2014, 14(11), 709-721.
[http://dx.doi.org/10.1038/nrc3803] [PMID: 25342630]
[11]
Wallace, D.C. Mitochondria and cancer. Nat. Rev. Cancer, 2012, 12(10), 685-698.
[http://dx.doi.org/10.1038/nrc3365] [PMID: 23001348]
[12]
Iommarini, L.; Ghelli, A.; Gasparre, G.; Porcelli, A.M. Mitochondrial metabolism and energy sensing in tumor progression. Biochim. Biophys. Acta Bioenerg., 2017, 1858(8), 582-590.
[http://dx.doi.org/10.1016/j.bbabio.2017.02.006] [PMID: 28213331]
[13]
Sullivan, L.B.; Chandel, N.S. Mitochondrial reactive oxygen species and cancer. Cancer Metab., 2014, 2, 17.
[http://dx.doi.org/10.1186/2049-3002-2-17] [PMID: 25671107]
[14]
Lenaz, G. Mitochondria and reactive oxygen species. Which role in physiology and pathology? Adv. Exp. Med. Biol., 2012, 942, 93-136.
[http://dx.doi.org/10.1007/978-94-007-2869-1_5] [PMID: 22399420]
[15]
Scatena, R. Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation. Adv. Exp. Med. Biol., 2012, 942, 287-308.
[http://dx.doi.org/10.1007/978-94-007-2869-1_13] [PMID: 22399428]
[16]
Idelchik, M.D.P.S.; Begley, U.; Begley, T.J.; Melendez, J.A. Mitochondrial ROS control of cancer. Semin. Cancer Biol., 2017, 47, 57-66.
[http://dx.doi.org/10.1016/j.semcancer.2017.04.005] [PMID: 28445781]
[17]
Bedard, K.; Krause, K.H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol. Rev., 2007, 87(1), 245-313.
[http://dx.doi.org/10.1152/physrev.00044.2005] [PMID: 17237347]
[18]
Nisimoto, Y.; Diebold, B.A.; Cosentino-Gomes, D.; Lambeth, J.D. Nox4: a hydrogen peroxide-generating oxygen sensor. Biochemistry, 2014, 53(31), 5111-5120.
[http://dx.doi.org/10.1021/bi500331y] [PMID: 25062272]
[19]
Guichard, C.; Pedruzzi, E.; Fay, M.; Ben Mkaddem, S.; Coant, N.; Daniel, F.; Ogier-Denis, E. [The Nox/Duox family of ROS-generating NADPH oxidases]. Med. Sci. (Paris), 2006, 22(11), 953-959.
[http://dx.doi.org/10.1051/medsci/20062211953] [PMID: 17101097]
[20]
Sies, H. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. Redox Biol., 2017, 11, 613-619.
[http://dx.doi.org/10.1016/j.redox.2016.12.035] [PMID: 28110218]
[21]
Brand, M.D. The sites and topology of mitochondrial superoxide production. Exp. Gerontol., 2010, 45(7-8), 466-472.
[http://dx.doi.org/10.1016/j.exger.2010.01.003] [PMID: 20064600]
[22]
Schafer, F.Q.; Buettner, G.R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic. Biol. Med., 2001, 30(11), 1191-1212.
[http://dx.doi.org/10.1016/S0891-5849(01)00480-4] [PMID: 11368918]
[23]
Wong, H.S.; Dighe, P.A.; Mezera, V.; Monternier, P.A.; Brand, M.D. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J. Biol. Chem., 2017, 292(41), 16804-16809.
[http://dx.doi.org/10.1074/jbc.R117.789271] [PMID: 28842493]
[24]
Sarti, P.; Arese, M.; Forte, E.; Giuffrè, A.; Mastronicola, D. Mitochondria and nitric oxide: chemistry and pathophysiology. Adv. Exp. Med. Biol., 2012, 942, 75-92.
[http://dx.doi.org/10.1007/978-94-007-2869-1_4] [PMID: 22399419]
[25]
Brand, M.D. Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic. Biol. Med., 2016, 100, 14-31.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.001] [PMID: 27085844]
[26]
Finkel, T. From sulfenylation to sulfhydration: what a thiolate needs to tolerate. Sci. Signal., 2012, 5(215), pe10.
[http://dx.doi.org/10.1126/scisignal.2002943] [PMID: 22416275]
[27]
Rhee, S.G.; Bae, Y.S.; Lee, S.R.; Kwon, J. Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci. STKE, 2000, 2000(53), pe1.
[http://dx.doi.org/10.1126/stke.2000.53.pe1] [PMID: 11752613]
[28]
Pan, Y.; Mansfield, K.D.; Bertozzi, C.C.; Rudenko, V.; Chan, D.A.; Giaccia, A.J.; Simon, M.C. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol. Cell. Biol., 2007, 27(3), 912-925.
[http://dx.doi.org/10.1128/MCB.01223-06] [PMID: 17101781]
[29]
Chen, Y.; McMillan-Ward, E.; Kong, J.; Israels, S.J.; Gibson, S.B. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J. Cell Sci., 2007, 120(Pt 23), 4155-4166.
[http://dx.doi.org/10.1242/jcs.011163] [PMID: 18032788]
[30]
West, A.P.; Brodsky, I.E.; Rahner, C.; Woo, D.K.; Erdjument-Bromage, H.; Tempst, P.; Walsh, M.C.; Choi, Y.; Shadel, G.S.; Ghosh, S. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature, 2011, 472(7344), 476-480.
[http://dx.doi.org/10.1038/nature09973] [PMID: 21525932]
[31]
Chandel, N.S.; Schumacker, P.T.; Arch, R.H. Reactive oxygen species are downstream products of TRAF-mediated signal transduction. J. Biol. Chem., 2001, 276(46), 42728-42736.
[http://dx.doi.org/10.1074/jbc.M103074200] [PMID: 11559697]
[32]
Zhou, R.; Yazdi, A.S.; Menu, P.; Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature, 2011, 469(7329), 221-225.
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[33]
Li, Q.; Gao, Z.; Chen, Y.; Guan, M.X. The role of mitochondria in osteogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells. Protein Cell, 2017, 8(6), 439-445.
[http://dx.doi.org/10.1007/s13238-017-0385-7] [PMID: 28271444]
[34]
Khacho, M.; Slack, R.S. Mitochondrial and reactive oxygen species signaling coordinate stem cell fate decisions and life long maintenance. Antioxid. Redox Signal., 2017.
[http://dx.doi.org/10.1089/ars.2017.7228] [PMID: 28657337]
[35]
Owusu-Ansah, E.; Banerjee, U. Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature, 2009, 461(7263), 537-541.
[http://dx.doi.org/10.1038/nature08313] [PMID: 19727075]
[36]
Tormos, K.V.; Anso, E.; Hamanaka, R.B.; Eisenbart, J.; Joseph, J.; Kalyanaraman, B.; Chandel, N.S. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab., 2011, 14(4), 537-544.
[http://dx.doi.org/10.1016/j.cmet.2011.08.007] [PMID: 21982713]
[37]
Sena, L.A.; Chandel, N.S. Physiological roles of mitochondrial reactive oxygen species. Mol. Cell, 2012, 48(2), 158-167.
[http://dx.doi.org/10.1016/j.molcel.2012.09.025] [PMID: 23102266]
[38]
Pan, Y.; Shadel, G.S. Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density. Aging (Albany NY), 2009, 1(1), 131-145.
[http://dx.doi.org/10.18632/aging.100016] [PMID: 20157595]
[39]
Mesquita, A.; Weinberger, M.; Silva, A.; Sampaio-Marques, B.; Almeida, B.; Leão, C.; Costa, V.; Rodrigues, F.; Burhans, W.C.; Ludovico, P. Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity. Proc. Natl. Acad. Sci. USA, 2010, 107(34), 15123-15128.
[http://dx.doi.org/10.1073/pnas.1004432107] [PMID: 20696905]
[40]
Schaar, C.E.; Dues, D.J.; Spielbauer, K.K.; Machiela, E.; Cooper, J.F.; Senchuk, M.; Hekimi, S.; Van Raamsdonk, J.M. Mitochondrial and cytoplasmic ROS have opposing effects on lifespan. PLoS Genet., 2015, 11(2)e1004972
[http://dx.doi.org/10.1371/journal.pgen.1004972] [PMID: 25671321]
[41]
Ralph, S.J.; Rodríguez-Enríquez, S.; Neuzil, J.; Saavedra, E.; Moreno-Sánchez, R. The causes of cancer revisited: “mitochondrial malignancy” and ROS-induced oncogenic transformation - why mitochondria are targets for cancer therapy. Mol. Aspects Med., 2010, 31(2), 145-170.
[http://dx.doi.org/10.1016/j.mam.2010.02.008] [PMID: 20206201]
[42]
Donley, N.; Thayer, M.J. DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability. Semin. Cancer Biol., 2013, 23(2), 80-89.
[http://dx.doi.org/10.1016/j.semcancer.2013.01.001] [PMID: 23327985]
[43]
Döppler, H; Storz, P. Mitochondrial and oxidative stressmediated activation of protein kinase d1 and its importance in pancreatic cancer. Front Oncol., 7, 41.
[http://dx.doi.org/10.3389/fonc.2017.00041] [PMID: 28361035]
[44]
Scatena, R.; Bottoni, P.; Giardina, B. Modulation of cancer cell line differentiation: A neglected proteomic analysis with potential implications in pathophysiology, diagnosis, prognosis, and therapy of cancer. Proteomics Clin. Appl., 2008, 2(2), 229-237.
[http://dx.doi.org/10.1002/prca.200780014] [PMID: 21136827]
[45]
Bottoni, P.; Giardina, B.; Vitali, A.; Boninsegna, A.; Scatena, R. A proteomic approach to characterizing ciglitazone-induced cancer cell differentiation in Hep-G2 cell line. Biochim. Biophys. Acta, 2009, 1794(4), 615-626.
[http://dx.doi.org/10.1016/j.bbapap.2009.01.006] [PMID: 19336041]
[46]
Yang, Y.; Karakhanova, S.; Hartwig, W.; D’Haese, J.G.; Philippov, P.P.; Werner, J.; Bazhin, A.V. Mitochondria and mitochondrial ROS in cancer: novel targets for anticancer therapy. J. Cell. Physiol., 2016, 231(12), 2570-2581.
[http://dx.doi.org/10.1002/jcp.25349] [PMID: 26895995]
[47]
Chandel, N.S.; Tuveson, D.A. The promise and perils of antioxidants for cancer patients. N. Engl. J. Med., 2014, 371(2), 177-178.
[http://dx.doi.org/10.1056/NEJMcibr1405701] [PMID: 25006725]
[48]
Saso, L.; Korkina, L.; Zarkovic, N. modulation of oxidative stress: pharmaceutical and pharmacological aspects 2017. Oxid. Med. Cell. Longev., 2017, 20174802824
[http://dx.doi.org/10.1155/2017/4802824] [PMID: 29391925]
[49]
Cheng, G.; Zielonka, J.; McAllister, D.M.; Mackinnon, A.C., Jr; Joseph, J.; Dwinell, M.B.; Kalyanaraman, B. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death. BMC Cancer, 2013, 13, 285.
[http://dx.doi.org/10.1186/1471-2407-13-285] [PMID: 23764021]
[50]
Cortés-Jofré, M.; Rueda, J.R.; Corsini-Muñoz, G.; Fonseca-Cortés, C.; Caraballoso, M.; Bonfill Cosp, X. Drugs for preventing lung cancer in healthy people. Cochrane Database Syst. Rev., 2012, 10CD002141
[http://dx.doi.org/10.1002/14651858.CD002141.pub2] [PMID: 23076895]
[51]
Evans, J.M.; Donnelly, L.A.; Emslie-Smith, A.M.; Alessi, D.R.; Morris, A.D. Metformin and reduced risk of cancer in diabetic patients. BMJ, 2005, 330(7503), 1304-1305.
[http://dx.doi.org/10.1136/bmj.38415.708634.F7] [PMID: 15849206]
[52]
Libby, G.; Donnelly, L.A.; Donnan, P.T.; Alessi, D.R.; Morris, A.D.; Evans, J.M. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care, 2009, 32(9), 1620-1625.
[http://dx.doi.org/10.2337/dc08-2175] [PMID: 19564453]
[53]
Decensi, A.; Puntoni, M.; Goodwin, P.; Cazzaniga, M.; Gennari, A.; Bonanni, B.; Gandini, S. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev. Res. (Phila.), 2010, 3(11), 1451-1461.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0157] [PMID: 20947488]
[54]
Xu, G.; Wu, H.; Zhang, J.; Li, D.; Wang, Y.; Wang, Y.; Zhang, H.; Lu, L.; Li, C.; Huang, S.; Xing, Y.; Zhou, D.; Meng, A. Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice. Free Radic. Biol. Med., 2015, 87, 15-25.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.05.045] [PMID: 26086617]
[55]
Cahova, M.; Palenickova, E.; Dankova, H.; Sticova, E.; Burian, M.; Drahota, Z.; Cervinkova, Z.; Kucera, O.; Gladkova, C.; Stopka, P.; Krizova, J.; Papackova, Z.; Oliyarnyk, O.; Kazdova, L. Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation. Am. J. Physiol. Gastrointest. Liver Physiol., 2015, 309(2), G100-G111.
[http://dx.doi.org/10.1152/ajpgi.00329.2014] [PMID: 26045616]
[56]
Batchuluun, B.; Inoguchi, T.; Sonoda, N.; Sasaki, S.; Inoue, T.; Fujimura, Y.; Miura, D.; Takayanagi, R. Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells. Atherosclerosis, 2014, 232(1), 156-164.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.10.025] [PMID: 24401231]
[57]
Najafi, M.; Cheki, M.; Rezapoor, S.; Geraily, G.; Motevaseli, E.; Carnovale, C.; Clementi, E.; Shirazi, A. Metformin: Prevention of genomic instability and cancer: A review. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2018, 827, 1-8.
[http://dx.doi.org/10.1016/j.mrgentox.2018.01.007] [PMID: 29502733]
[58]
Pernicova, I.; Korbonits, M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat. Rev. Endocrinol., 2014, 10(3), 143-156.
[http://dx.doi.org/10.1038/nrendo.2013.256] [PMID: 24393785]
[59]
Scatena, R.; Bottoni, P.; Martorana, G.E.; Ferrari, F.; De Sole, P.; Rossi, C.; Giardina, B. Mitochondrial respiratory chain dysfunction, a non-receptor-mediated effect of synthetic PPAR-ligands: biochemical and pharmacological implications. Biochem. Biophys. Res. Commun., 2004, 319(3), 967-973.
[http://dx.doi.org/10.1016/j.bbrc.2004.05.072] [PMID: 15184076]
[60]
Scatena, R.; Bottoni, P.; Vincenzoni, F.; Messana, I.; Martorana, G.E.; Nocca, G.; De Sole, P.; Maggiano, N.; Castagnola, M.; Giardina, B. Bezafibrate induces a mitochondrial derangement in human cell lines: a PPAR-independent mechanism for a peroxisome proliferator. Chem. Res. Toxicol., 2003, 16(11), 1440-1447.
[http://dx.doi.org/10.1021/tx0341052] [PMID: 14615970]
[61]
Prost, S.; Relouzat, F.; Spentchian, M.; Ouzegdouh, Y.; Saliba, J.; Massonnet, G.; Beressi, J.P.; Verhoeyen, E.; Raggueneau, V.; Maneglier, B.; Castaigne, S.; Chomienne, C.; Chrétien, S.; Rousselot, P.; Leboulch, P. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature, 2015, 525(7569), 380-383.
[http://dx.doi.org/10.1038/nature15248] [PMID: 26331539]
[62]
Pérez-Ortiz, J.M.; Tranque, P.; Burgos, M.; Vaquero, C.F.; Llopis, J. Glitazones induce astroglioma cell death by releasing reactive oxygen species from mitochondria: modulation of cytotoxicity by nitric oxide. Mol. Pharmacol., 2007, 72(2), 407-417.
[http://dx.doi.org/10.1124/mol.106.032458] [PMID: 17504946]
[63]
Shishido, S.; Koga, H.; Harada, M.; Kumemura, H.; Hanada, S.; Taniguchi, E.; Kumashiro, R.; Ohira, H.; Sato, Y.; Namba, M.; Ueno, T.; Sata, M. Hydrogen peroxide overproduction in megamitochondria of troglitazone-treated human hepatocytes. Hepatology, 2003, 37(1), 136-147.
[http://dx.doi.org/10.1053/jhep.2003.50014] [PMID: 12500198]
[64]
Srivastava, N.; Kollipara, R.K.; Singh, D.K.; Sudderth, J.; Hu, Z.; Nguyen, H.; Wang, S.; Humphries, C.G.; Carstens, R.; Huffman, K.E.; DeBerardinis, R.J.; Kittler, R. Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels. Cell Metab., 2014, 20(4), 650-661.
[http://dx.doi.org/10.1016/j.cmet.2014.08.003] [PMID: 25264247]
[65]
Cramer, S.L.; Saha, A.; Liu, J.; Tadi, S.; Tiziani, S.; Yan, W.; Triplett, K.; Lamb, C.; Alters, S.E.; Rowlinson, S.; Zhang, Y.J.; Keating, M.J.; Huang, P.; DiGiovanni, J.; Georgiou, G.; Stone, E. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat. Med., 2017, 23(1), 120-127.
[http://dx.doi.org/10.1038/nm.4232] [PMID: 27869804]

Rights & Permissions Print Cite
Article Metrics
56
© 2024 Bentham Science Publishers | Privacy Policy