The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

Stéphanie A. Castaldo1, Juliana Crês de Freitas1, Nadine V. Conchinha1, Patrícia A. Madureira1
1Centre for Biomedical Research (CBMR), University of Algarve, Campus of Gambelas, Building 8, Room 2.22, 8055-139 Faro, Portugal

Tóm tắt

The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.

Từ khóa


Tài liệu tham khảo

10.1074/jbc.m603761200

10.1016/j.bbamem.2006.02.015

10.1126/science.1130481

10.1016/j.taap.2012.08.005

10.1089/ars.2013.5330

10.1073/pnas.1005776107

10.1016/j.molcel.2007.03.016

10.1089/ars.2007.1957

10.3390/ijms14023568

10.1016/s0027-5107(01)00091-4

10.1016/0003-9861(84)90010-9

10.1158/0008-5472.can-07-5259

10.1126/science.1156906

10.1007/s00018-009-0099-y

10.1128/MCB.02265-06

10.1023/b:cbto.0000004952.07979.3d

10.18632/oncotarget.463

10.1155/2013/972913

10.1016/j.ccr.2011.08.024

10.1038/nature10189

10.1038/nrm3801

10.2741/1667

10.1074/jbc.m002740200

10.1038/20459

10.1006/bbrc.1999.0878

10.1128/MCB.18.7.4089

10.1038/sj.cdd.4402307

10.1016/j.semcancer.2013.08.007

10.1083/jcb.200609074

10.1074/jbc.m001914200

10.1016/j.ccr.2007.08.004

10.1016/j.cmet.2005.05.001

10.1161/01.ATV.0000258979.92828.bc

10.1042/BJ20081386

10.3109/10715761003667554

10.1016/j.exger.2010.01.003

10.1016/j.bbamcr.2006.09.006

10.1089/ars.2007.1782

10.3390/ijms14023683

10.1038/nrc1782

10.1097/00062752-199502010-00008

Cui S., 1994, Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms, Cancer Research, 54, 2462

10.1038/nrd2222

10.1080/09553009414550041

10.1177/0192623309356453

10.1038/nrd4002

10.1007/s13277-013-0804-1

10.1016/j.cbi.2005.12.009

10.1002/cbf.1275

10.4161/oxim.3.1.10095

10.1080/10408360500523878

10.1016/0959-8049(96)00051-2

10.1016/s0009-2797(98)00008-8

10.1186/1471-2407-9-56

10.1016/j.bbcan.2010.07.004

10.3892/ijo.2011.986

10.1016/j.ccell.2014.11.019

10.18632/oncotarget.375

10.18632/oncoscience.12

10.1046/j.1432-1327.2000.01701.x

10.1093/emboj/17.9.2596

10.1126/science.275.5296.90

10.1093/embo-reports/kve046

10.1016/s0891-5849(00)00313-0

10.1182/blood.V89.7.2480

Kawahara N., 1996, Enhanced coexpression of thioredoxin and high mobility group protein 1 genes in human hepatocellular carcinoma and the possible association with decreased sensitivity to cisplatin, Cancer Research, 56, 5330

Yokomizo A., 1995, Cellular levels of thioredoxin associated with drug sensitivity to cisplatin, mitomycin C, doxorubicin, and etoposide, Cancer Research, 55, 4293

10.1016/j.mad.2004.08.012

Ho J. C.-M., 2001, Differential expression of manganese superoxide dismutase and catalase in lung cancer, Cancer Research, 61, 8578

10.1097/00029330-200712010-00006

10.1007/s005350050181

Janssen A. M. L., 2000, Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer, Clinical Cancer Research, 6, 3183

Salzman R., 2007, Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases, Neoplasma, 54, 321

10.1006/jsre.1999.5773

10.1016/j.freeradbiomed.2015.04.001

Nelson K. K., 2003, Elevated Sod2 activity augments matrix metalloproteinase expression: evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis, Clinical Cancer Research, 9, 424

10.1074/jbc.M100199200

10.1016/j.febslet.2007.08.021

Cullen J. J., 2003, The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma, Cancer Research, 63, 1297

10.1074/jbc.m503296200

Oberley L. W., 1979, Role of superoxide dismutase in cancer: a review, Cancer Research, 39, 1141

10.1002/path.946

10.1128/MCB.25.17.7758-7769.2005

10.1016/j.biopha.2005.03.006

10.1089/152308604773934260

10.1089/ars.2006.8.1283

10.1002/(sici)1097-0045(19980515)35:3lt;221::aid-pros8>3.0.co;2-j

10.1073/pnas.68.5.1024

10.1042/bj0600310

10.1016/0005-2744(70)90052-5

10.1074/jbc.m503991200

10.1016/j.jinorgbio.2009.07.011

10.1515/BC.2010.068

10.1016/s0891-5849(00)00512-8

10.1016/s0891-5849(98)00092-6

10.1111/j.1432-1033.1995.tb20798.x

10.1007/s13277-014-2714-2

10.1158/1078-0432.ccr-06-2082

10.1097/00008390-199810000-00001

10.1002/ijc.22493

Bechtel W., 2009, Modulation of intercellular ROS signaling of human tumor cells, Anticancer Research, 29, 4559

Bechtel W., 2009, Catalase protects tumor cells from apoptosis induction by intercellular ROS signaling, Anticancer Research, 29, 4541

Bauer G., 2000, Reactive oxygen and nitrogen species: efficient, selective, and interactive signals during intercellular induction of apoptosis, Anticancer Research, 20, 4115

Bauer G., 2012, Tumor cell-protective catalase as a novel target for rational therapeutic approaches based on specific intercellular ROS signaling, Anticancer Research, 32, 2599

10.1515/hsz-2014-0234

10.3892/ijo.2014.2398

10.1038/bjc.2013.396

10.1155/2014/715867

10.3164/jcbn.11-109

10.1016/j.fob.2012.12.002

10.1111/j.1440-1843.2006.00849.x

10.1002/path.1042

10.1016/j.bbapap.2014.11.011

10.2147/bctt.s61281

10.1016/j.mam.2007.04.005

10.1074/jbc.m114.621995

10.3892/ijo_00000369

10.1074/jbc.m705929200

Wei S. J., 2000, Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation, Cancer Research, 60, 6688

10.1021/jm500865u

10.3892/ijo.2014.2589

Bobola M. S., 2001, Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas, Clinical Cancer Research, 7, 3510

10.1002/ijc.25900

10.1111/j.1751-2980.2010.00442.x

10.1016/j.canlet.2004.11.007

10.1089/ars.2008.2226

10.1016/j.freeradbiomed.2013.06.041

10.1002/jcp.20246

10.2174/09298673113209990154

10.1016/j.redox.2012.10.001

10.1002/path.2653

10.1073/pnas.0806268105

10.1016/j.tibs.2008.12.008

10.1158/0008-5472.can-05-1997

10.1016/j.freeradbiomed.2011.09.035

10.1038/sj.onc.1207137

10.1074/jbc.m207509200

10.1016/j.cell.2011.07.032

10.1189/jlb.1202629

10.1016/j.canlet.2008.03.035

10.1517/14728222.2013.772136

10.1038/sj.onc.1203159

10.1002/ijc.23754

10.1016/j.freeradbiomed.2011.05.018

10.1126/scitranslmed.3007653

10.1126/scitranslmed.3008488

10.1126/scitranslmed.3007154

10.1007/s12094-013-1028-y

10.3892/or.2015.3837

10.4149/neo_2014_078

10.1182/blood-2011-06-334672

10.1667/rr3056.1

10.1371/journal.pone.0050591

10.1073/pnas.0402959101

10.1016/j.bbrc.2004.03.110

10.1016/j.neures.2010.04.002

10.3892/ijo-00000451

10.1371/journal.pbio.0020362

10.1074/jbc.m507124200

10.1074/jbc.m806902200

10.1073/pnas.0607260103

10.1002/cbf.2949

10.18632/oncotarget.3841

10.1002/jcp.24957

10.1016/j.freeradbiomed.2014.03.026

10.1016/j.phytochem.2014.09.001

10.1146/annurev.pharmtox.44.101802.121851

10.1016/j.bbagen.2014.10.008

10.1016/j.tiv.2011.05.006

10.1016/j.ejmech.2013.12.015

10.1038/onc.2009.47

10.1042/bj20021469

10.3892/or_00000392

10.1016/j.febslet.2010.05.054

10.1016/j.lfs.2013.12.009

10.1007/s12079-007-0006-y

10.1002/ijc.21685

10.1158/0008-5472.can-06-3914

10.1016/j.toxlet.2012.02.020

10.1159/000373938

10.1371/journal.pone.0070956

10.1016/j.bbabio.2015.02.012

10.1016/j.freeradbiomed.2007.03.020

10.1038/sj.onc.1206940

10.1021/bi00607a008

10.7164/antibiotics.33.426

10.3109/10715762.2013.819974

10.1007/s10495-007-0082-8

10.1016/j.bbrc.2006.06.140

10.1242/jcs.092098

10.1002/jcp.20638

10.1073/pnas.1404182111

10.1124/pr.56.2.6

10.1096/fasebj.4.13.2210154

10.1016/j.yjmcc.2006.06.009

10.1016/j.bbabio.2012.09.016

10.1007/s00280-015-2739-2

10.1074/jbc.m113.484576

10.1016/j.bbamcr.2007.05.002

10.1007/s11515-012-1204-4

10.1016/j.tiv.2013.11.006

10.3892/etm.2011.304