Login Register Cart 0
Review Article

癌症中复杂的线粒体代谢：创新的药理学方法

卷 27, 期 13, 2020

页: [2106 - 2117] 页: 12

弟呕挨: 10.2174/0929867326666190823163009

价格: $65

摘要

背景：线粒体在癌症中显着地发挥着重要的和不同的致病作用（即维持特定的新陈代谢，激活信号传导途径，促进细胞凋亡抗性，促进癌细胞的传播并最终促进基因组的不稳定性）。有趣的是，所有这些作用似乎都与线粒体的基本活性有关，即氧化代谢。有趣的是，线粒体氧化代谢和活性氧产生/中和的典型修饰似乎在癌症中所有这些复杂的致病作用中都起着核心作用。在这些基础上，对癌症和线粒体之间分子关系的仔细理解可能代表了实现阻止典型癌症进展的治疗方法的基本步骤。 这项审查的主要目的是强调癌细胞的氧化线粒体代谢的一些被忽略的方面，以促进具有诊断和治疗潜力的更多翻译研究。 方法：我们回顾了有关线粒体在癌症中的各种作用的临床和实验研究的现有文献，并关注了癌细胞的线粒体代谢。 结果：线粒体是活性氧的重要来源。它们的毒性作用似乎在癌细胞中增加。但是，尚不清楚损害是否取决于ROS过量生产和/或排毒缺陷。这两个过程的失败可能是癌症过程的关键组成部分，并且与癌细胞的实际微环境严格相关。 结论：线粒体也通过ROS产生，在促进和维持癌症及其扩散中具有基本的致病作用。仔细了解癌细胞线粒体的纠结氧化还原状态代表了实现阻止典型癌症进展的治疗方法的基本步骤。

关键词: 分子疗法，线粒体，ROS，癌症，新陈代谢，抗氧化剂，氧化应激，诊断性生物标志物。

« 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