title: The role of antioxidants in the era of cardio‑oncology.
abstract: Although most chemotherapeutic drugs have the potential to exert cardiotoxicity, these drugs have been chosen for use in cancer treatment because survival and curability benefits outweigh the risk of these complications. Anthracyclines, for example, are a powerful class of chemotherapeutic agents; however, their use is restricted by dose-related cardiotoxicity. Experimental evidence strongly supports the role of reactive oxygen species in this process, suggesting that antioxidants may be effective in protecting the heart from toxicity. Clinical use of antioxidants to protect the heart during anthracycline chemotherapy has been controversial due to the potential for reduced cytotoxic efficacy toward cancer cells. Results from randomized clinical trials addressing whether antioxidants either reduce the incidence of clinical heart failure among patients undergoing anthracycline-based chemotherapy or reduce the response rates to anthracycline-based chemotherapy have been unclear. While anthracyclines are by far the most well-studied antitumor agents with cardiotoxic properties, evidence now shows that reactive oxygen species may play roles in cardiotoxicity induced by other chemotherapeutic agents such as cyclophosphamide, cisplatin, 5-fluorouracil, and trastuzumab. Thus, in the new era of combination therapy and long-term survival of cancer patients, the use of antioxidants to support cancer therapy should be revisited.
authors: Duncan T
authors: DT
authors: Vincent
authors: Yasmine F
authors: YF
authors: Ibrahim
authors: Michael Graham
authors: MG
authors: Espey
authors: Yuichiro J
authors: YJ
authors: Suzuki
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015996:Survival Rate
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species
references: Cancer Chemother Rep. 1975 Jul-Aug;59(4):689-95
references: 1175163
references: Eur J Cancer. 1999 Nov;35(12):1688-92
references: 10674014
references: Med Oncol Tumor Pharmacother. 1988;5(3):159-63
references: 3137399
references: Cancer Biother Radiopharm. 2009 Dec;24(6):675-80
references: 20025547
references: Biochemistry. 1979 Sep 4;18(18):4024-30
references: 486409
references: Pediatr Hematol Oncol. 2007 Sep;24(6):403-8
references: 17710657
references: Life Sci. 1999;65(12):1265-74
references: 10503942
references: Antioxid Redox Signal. 2001 Feb;3(1):135-45
references: 11291592
references: Breast Cancer Res Treat. 2012 Feb;132(1):109-19
references: 21559822
references: Am J Clin Nutr. 1991 Dec;54(6 Suppl):1298S-1301S
references: 1962586
references: J Biol Chem. 2009 Jan 23;284(4):2080-7
references: 19017630
references: Transplant Proc. 1971 Mar;3(1):400-4
references: 4398496
references: Cancer. 1973 Aug;32(2):302-14
references: 4353012
references: Pharmacol Ther. 1990;47(2):219-31
references: 2203071
references: Circulation. 1994 Jun;89(6):2829-35
references: 8205698
references: Biochem Pharmacol. 1999 Apr 1;57(7):727-41
references: 10075079
references: J Toxicol Environ Health A. 2000 Apr 14;59(7):585-9
references: 10777249
references: Drug Saf. 2000 Apr;22(4):263-302
references: 10789823
references: Mol Cell Biochem. 2011 Jan;347(1-2):41-51
references: 20936496
references: Clin Cancer Res. 2003 Nov 1;9(14):5078-84
references: 14613984
references: J Mol Cell Cardiol. 2006 Nov;41(5):845-54
references: 17005195
references: Ann Intern Med. 1996 Jul 1;125(1):47-58
references: 8644988
references: J Clin Invest. 1980 Jan;65(1):128-35
references: 7350193
references: FASEB J. 1997 Oct;11(12):931-6
references: 9337145
references: Oxid Med Cell Longev. 2010 Sep-Oct;3(5):308-16
references: 21150336
references: Lancet Oncol. 2010 Oct;11(10):950-61
references: 20850381
references: Semin Oncol. 1983 Mar;10(1 Suppl 1):53-5
references: 6340204
references: Bone Marrow Transplant. 2001 Jul;28(1):101-3
references: 11498753
references: Cancer Res. 1986 May;46(5):2551-6
references: 3697994
references: J Clin Oncol. 1996 Feb;14(2):362-72
references: 8636745
references: Cardiovasc Hematol Agents Med Chem. 2006 Jan;4(1):1-5
references: 16529545
references: J Am Soc Echocardiogr. 2011 Jun;24(6):699-705
references: 21353471
references: Cancer. 2002 Oct 1;95(7):1592-600
references: 12237930
references: Mol Aspects Med. 1994;15 Suppl:s207-12
references: 7752832
references: Ann Oncol. 2006 Apr;17(4):614-22
references: 16423847
references: Lancet. 2005 May 14-20;365(9472):1687-717
references: 15894097
references: J Clin Oncol. 1998 Jan;16(1):86-92
references: 9440727
references: J Pharmacol Exp Ther. 1994 Apr;269(1):430-6
references: 8169849
references: Pharmacol Res. 2006 Mar;53(3):278-86
references: 16436331
references: Anticancer Res. 1998 Nov-Dec;18(6A):4387-92
references: 9891497
references: J Clin Oncol. 1997 Apr;15(4):1318-32
references: 9193323
references: Acta Oncol. 2003;42(4):304-8
references: 12899501
references: Clin Cancer Res. 1997 Oct;3(10):1747-54
references: 9815559
references: Life Sci. 2007 May 1;80(21):1993-8
references: 17418239
references: J Am Coll Cardiol. 2006 Dec 5;48(11):2258-62
references: 17161256
references: Science. 1989 May 12;244(4905):707-12
references: 2470152
references: Eur J Pharmacol. 2006 Aug 14;543(1-3):92-6
references: 16814280
references: Int J Hematol. 2008 Sep;88(2):227-236
references: 18548196
references: Cancer Treat Rep. 1978 Jul;62(7):1005-8
references: 688243
references: Biochem Biophys Res Commun. 2004 Jun 18;319(1):1-11
references: 15158434
references: J Clin Oncol. 1992 Jan;10(1):117-27
references: 1727913
references: Cancer Res. 1981 Sep;41(9 Pt 1):3436-40
references: 6790165
references: J Pharmacol Exp Ther. 2007 Feb;320(2):790-800
references: 17135345
references: Blood. 2009 Sep 3;114(10):2051-9
references: 19584400
references: Clin Cardiol. 2011 Jun;34(6):356-9
references: 21538392
references: Hum Exp Toxicol. 2004 May;23(5):251-6
references: 15222403
references: J Exp Clin Cancer Res. 2012 Jul 19;31:60
references: 22812382
references: Res Commun Chem Pathol Pharmacol. 1979 May;24(2):401-4
references: 461995
references: Cochrane Database Syst Rev. 2011 Jun 15;(6):CD003917
references: 21678342
references: Indian J Physiol Pharmacol. 1990 Apr;34(2):94-100
references: 2174831
references: Science. 1977 Jul 8;197(4299):165-7
references: 877547
references: J Cancer Res Clin Oncol. 2006 Feb;132(2):121-8
references: 16283381
references: Basic Clin Pharmacol Toxicol. 2005 Nov;97(5):311-9
references: 16236144
references: J Med Chem. 1991 Jan;34(1):298-302
references: 1992130
references: Cancer Lett. 1988 Aug 15;41(2):169-77
references: 2841019
references: BMC Cancer. 2011 Nov 02;11:471
references: 22044845
references: Biomed Pharmacother. 2005 Dec;59(10):541-4
references: 16325366
references: Cancer Chemother Pharmacol. 1995;37(1-2):55-62
references: 7497597
references: J Mol Cell Cardiol. 1995 Apr;27(4):1055-63
references: 7563102
references: Toxicol Appl Pharmacol. 2004 Oct 15;200(2):159-68
references: 15476868
references: J Natl Cancer Inst. 2010 Jan 6;102(1):14-25
references: 20007921
references: J Clin Oncol. 2002 Mar 1;20(5):1215-21
references: 11870163
references: Drug Discov Ther. 2012 Jun;6(3):147-56
references: 22890205
references: Am Heart J. 1986 Jan;111(1):95-102
references: 3946165
references: Arch Intern Med. 1981 May;141(6):758-63
references: 7235784
references: Mol Cell Biochem. 1999 Jun;196(1-2):43-9
references: 10448901
references: Haematol Blood Transfus. 1990;33:566-70
references: 2182448
references: Eur J Pharmacol. 2011 Jan 10;650(1):335-41
references: 21034734
references: Biochemistry. 1984 Feb 28;23(5):928-36
references: 6324858
references: Biophys Chem. 1990 Apr;35(2-3):247-57
references: 2204444
references: Praxis (Bern 1994). 1995 Oct 24;84(43):1220-3
references: 7481338
references: Breast Cancer Res Treat. 2009 Sep;117(2):357-64
references: 19082707
references: Lab Invest. 1983 Jul;49(1):69-77
references: 6408310
references: Expert Opin Drug Saf. 2003 Jan;2(1):59-71
references: 12904125
references: N Engl J Med. 2001 Mar 15;344(11):783-92
references: 11248153
references: Circulation. 2000 Oct 24;102(17):2105-10
references: 11044428
references: J Pineal Res. 2011 Jan;50(1):89-96
references: 21062350
references: N Engl J Med. 2004 Jul 8;351(2):145-53
references: 15247354
references: J Clin Oncol. 1996 Dec;14(12):3112-20
references: 8955656
references: J Natl Cancer Inst. 2009 May 6;101(9):644-50
references: 19401546
references: FEBS Lett. 1982 Aug 16;145(1):137-42
references: 6897044
references: Cancer Treat Rep. 1978 Jun;62(6):887-91
references: 667863
references: Cancer Chemother Pharmacol. 1989;24(6):395-6
references: 2791194
references: J Pharmacol Exp Ther. 2010 Jul;334(1):2-8
references: 20335321
references: Cancer Treat Rep. 1979 Jan;63(1):89-92
references: 421236
references: Cancer Treat Rep. 1976 Jul;60(7):961-2
references: 1009530
references: J Pharmacol Exp Ther. 2006 Jul;318(1):424-33
references: 16614166
references: Toxicol Appl Pharmacol. 2010 Apr 1;244(1):4-15
references: 20122947
references: Biochim Biophys Acta. 1999 Apr 21;1411(1):201-5
references: 10216166
references: Food Chem Toxicol. 2009 Jun;47(6):1176-1183
references: 19425235
references: Exp Cell Res. 2007 May 1;313(8):1588-601
references: 17400210