title: Epigenetic effects of cadmium in cancer: focus on melanoma.
abstract: Cadmium is a highly toxic heavy metal, which has a destroying impact on organs. Exposure to cadmium causes severe health problems to human beings due to its ubiquitous environmental presence and features of the pathologies associated with pro-longed exposure. Cadmium is a well-established carcinogen, although the underlying mechanisms have not been fully under-stood yet. Recently, there has been considerable interest in the impact of this environmental pollutant on the epigenome. Be-cause of the role of epigenetic alterations in regulating gene expression, there is a potential for the integration of cadmium-induced epigenetic alterations as critical elements in the cancer risk assessment process. Here, after a brief review of the ma-jor diseases related to cadmium exposure, we focus our interest on the carcinogenic potential of this heavy metal. Among the several proposed pathogenetic mechanisms, particular attention is given to epigenetic alterations, including changes in DNA methylation, histone modifications and non-coding RNA expression. We review evidence for a link between cadmium-induced epigenetic changes and cell transformation, with special emphasis on melanoma. DNA methylation, with reduced expression of key genes that regulate cell proliferation and apoptosis, has emerged as a possible cadmium-induced epigenetic mechanism in melanoma. A wider comprehension of mechanisms related to this common environmental contaminant would allow a better cancer risk evaluation.
authors: Department of Experimental Specialistic Medical, Surgical and Odontostomatology Sciences, University of Messina, Messina, Italy.
authors: Mario
authors: M
authors: Venza
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Maria
authors: M
authors: Visalli
authors: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Messina, Italy.
authors: Carmelo
authors: C
authors: Biondo
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Rosaria
authors: R
authors: Oteri
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Federica
authors: F
authors: Agliano
authors: Department of Experimental Specialistic Medical, Surgical and Odontostomatology Sciences, University of Messina, Messina, Italy.
authors: Silvia
authors: S
authors: Morabito
authors: Department of Neurosciences, University of Messina, Messina, Italy.
authors: Gerardo
authors: G
authors: Caruso
authors: Department of Neurosciences, University of Messina, Messina, Italy.
authors: Maria
authors: M
authors: Caffo
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Diana
authors: D
authors: Teti
authors: Department of Experimental Specialistic Medical, Surgical and Odontostomatology Sciences, University of Messina, Messina, Italy.
authors: Isabella
authors: I
authors: Venza
keywords: Cadmium; Cancer; DNA methylation; Epigenetics; Histone modifications; Melanoma; Non-coding RNAs.
references: Nephrol Dial Transplant. 2002;17 Suppl 2:35-9
references: 11904357
references: Am J Hypertens. 2000 Feb;13(2):146-56
references: 10701814
references: Hum Exp Toxicol. 2001 Nov;20(11):577-83
references: 11926612
references: Toxicology. 2003 Nov 5;192(2-3):95-117
references: 14580780
references: Cell. 2012 Mar 16;148(6):1172-87
references: 22424228
references: Environ Health Perspect. 1997 Jul;105(7):712-6
references: 9294717
references: Toxicol Appl Pharmacol. 2009 Aug 1;238(3):192-200
references: 19341754
references: Toxicol Sci. 2006 Oct;93(2):322-30
references: 16854967
references: Scand J Work Environ Health. 2012 Sep;38(5):476-83
references: 22179223
references: Int J Oncol. 2014 Jul;45(1):57-66
references: 24819879
references: Somat Cell Mol Genet. 1990 Nov;16(6):529-37
references: 2267627
references: EMBO Rep. 2011 Jul 01;12(7):620-2
references: 21681201
references: Thorax. 2004 Mar;59(3):194-8
references: 14985551
references: Environ Health Perspect. 2002 Oct;110 Suppl 5:793-5
references: 12426133
references: Toxicol Sci. 2012 Feb;125(2):412-7
references: 22112500
references: J Hepatol. 2009 Apr;50(4):766-78
references: 19232449
references: Int J Biochem Cell Biol. 2010 Aug;42(8):1316-29
references: 19800023
references: IUBMB Life. 2006 May-Jun;58(5-6):312-7
references: 16754324
references: Toxicol Appl Pharmacol. 2000 May 1;164(3):291-300
references: 10799339
references: Environ Res. 2004 May;95(1):20-31
references: 15068927
references: J Physiol. 1988 Dec;407:433-52
references: 2855742
references: Carcinogenesis. 2007 Jun;28(6):1264-8
references: 17272309
references: Neurotoxicology. 2007 Jul;28(4):790-7
references: 17408746
references: Int Rev Cell Mol Biol. 2013;303:357-85
references: 23445815
references: J Neurosci. 1997 Jun 1;17(11):4180-9
references: 9151735
references: Toxicol Lett. 2003 Feb 3;137(3):135-41
references: 12523955
references: Epigenetics. 2013 Dec;8(12 ):1355-72
references: 24149212
references: J Environ Sci Health A Tox Hazard Subst Environ Eng. 2004;39(9):2507-15
references: 15478940
references: Adv Cancer Res. 2000;77:81-137
references: 10549356
references: MBio. 2014 Sep 09;5(5):e01428-14
references: 25205091
references: Toxicol Appl Pharmacol. 2000 May 1;164(3):321-9
references: 10799343
references: Clin Cancer Res. 2010 Mar 1;16(5):1682-9
references: 20179218
references: Occup Med (Lond). 2002 May;52(3):157-64
references: 12063361
references: Int J Oncol. 1997 Jan;10(1):141-6
references: 21533357
references: Mol Cell. 2004 Aug 27;15(4):585-94
references: 15327774
references: Aging Clin Exp Res. 2012 Feb;24(1):21-7
references: 21499024
references: Exp Dermatol. 2014 May;23(5):332-8
references: 24673285
references: Cell Cycle. 2012 Oct 1;11(19):3543-9
references: 22895111
references: Clin Cancer Res. 2007 Jun 1;13(11):3191-7
references: 17545522
references: Epigenetics. 2014 May;9(5):685-92
references: 24762620
references: J Inorg Biochem. 2000 Apr;79(1-4):241-4
references: 10830873
references: Toxicol Lett. 2012 Jul 7;212(1):66-74
references: 22613180
references: PLoS One. 2012;7(3):e33853
references: 22457795
references: Nat Med. 2000 May;6(5):529-35
references: 10802708
references: Eur J Cancer. 1996 Dec;32A(13):2342-7
references: 9038619
references: Environ Health Perspect. 2004 Jul;112(10):1099-103
references: 15238284
references: Clin Cancer Res. 2003 Dec 15;9(17):6401-9
references: 14695141
references: BMC Cancer. 2002 Nov 15;2:29
references: 12433278
references: Toxicol Appl Pharmacol. 1989 Dec;101(3):447-60
references: 2481347
references: Int J Biochem Cell Biol. 2004 Oct;36(10):1890-909
references: 15203104
references: J Immunol. 2012 Feb 15;188(4):1953-60
references: 22250086
references: Toxicology. 2002 Jan 15;170(1-2):111-7
references: 11750088
references: Am J Physiol Lung Cell Mol Physiol. 2001 Sep;281(3):L607-15
references: 11504687
references: Nat Med. 2003 Aug;9(8):1000-1
references: 12894163
references: Cancer Invest. 2005;23(3):256-63
references: 15945511
references: Gastroenterology. 1978 May;74(5 Pt 1):841-6
references: 640339
references: Eur Rev Med Pharmacol Sci. 2012 Oct;16(11):1506-12
references: 23111962
references: Toxicol Appl Pharmacol. 2003 Feb 1;186(3):163-88
references: 12620369
references: Int J Mol Med. 1998 Jun;1(6):1001-6
references: 9852638
references: Front Genet. 2014 Mar 18;5:54
references: 24672539
references: Environ Res. 2004 Jun;95(2):143-50
references: 15147919
references: Environ Health Perspect. 2002 Feb;110(2):151-5
references: 11836143
references: Int J Mol Sci. 2013 Aug 12;14(8):16600-16
references: 23941782
references: Toxicol Appl Pharmacol. 1990 Apr;103(2):255-70
references: 2330588
references: Environ Health Perspect. 2007 Oct;115(10):1454-9
references: 17938735
references: Endocr Relat Cancer. 2010 Jan 29;17(1):F19-36
references: 19779035
references: Am J Physiol Renal Physiol. 2006 May;290(5):F1074-82
references: 16263807
references: Biometals. 2004 Oct;17(5):513-8
references: 15688855
references: Histopathology. 1993 Sep;23(3):257-63
references: 8225244
references: J Environ Sci Eng. 2006 Apr;48(2):103-8
references: 17913185
references: Nature. 2007 May 24;447(7143):407-12
references: 17522673
references: Toxicol Lett. 2009 Jan 30;184(2):134-8
references: 19041697
references: Carcinogenesis. 1997 May;18(5):1021-6
references: 9163690
references: J Biol Chem. 1998 May 22;273(21):13245-54
references: 9582369
references: Cell Biol Toxicol. 2002;18(1):29-42
references: 11991084
references: Hum Exp Toxicol. 2003 Feb;22(2):57-63
references: 12693828
references: APMIS. 2004 Jul-Aug;112(7-8):508-25
references: 15563313
references: Am J Pathol. 1999 Sep;155(3):739-52
references: 10487832
references: Environ Health Perspect. 2005 Feb;113(2):164-9
references: 15687053
references: Cell Signal. 2003 Nov;15(11):1059-70
references: 14499349
references: Sci Total Environ. 2013 Jun 1;454-455:562-77
references: 23570911
references: ISRN Toxicol. 2014 Mar 13;2014:976428
references: 25101185
references: Mutat Res. 2013 Oct 9;757(2):125-31
references: 23948183
references: Oncogene. 2010 Apr 15;29(15):2302-8
references: 20190813
references: Epigenetics. 2012 Nov;7(11):1315-30
references: 23051921
references: Oncogene. 2001 Sep 13;20(41):5865-77
references: 11593392
references: Neurotoxicology. 1998 Aug-Oct;19(4-5):529-35
references: 9745907
references: Mutat Res. 2002 Mar;511(1):15-43
references: 11906840
references: Cell Signal. 2012 Feb;24(2):560-8
references: 22037550
references: Anticancer Res. 2010 Jul;30(7):2489-96
references: 20682973
references: Biol Trace Elem Res. 2006 Oct;113(1):35-44
references: 17114813
references: Chem Res Toxicol. 2008 Jan;21(1):28-44
references: 17970581
references: Occup Environ Med. 2002 Jun;59(6):394-6; discussion 397
references: 12040115
references: Epigenetics. 2012 Nov;7(11):1238-48
references: 22976526
references: Circ J. 2011;75(10):2491-5
references: 21799275
references: J Cell Sci. 1992 Dec;103 ( Pt 4):1073-81
references: 1487490
references: Nature. 1997 Oct 16;389(6652):753-8
references: 9338790
references: PLoS One. 2011;6(8):e23048
references: 21829690
references: FEBS J. 2013 Sep;280(18):4531-8
references: 23815091
references: Toxicology. 1999 Mar 1;133(1):43-58
references: 10413193
references: J Bone Miner Res. 2004 Jun;19(6):900-5
references: 15125789
references: Cancer Cell Int. 2011 Feb 08;11(1):2
references: 21303554
references: Molecules. 2011 Dec 15;16(12):10443-56
references: 22173337
references: ALTEX. 2012;29(2):173-82
references: 22562489
references: Chem Res Toxicol. 2010 Feb 15;23(2):432-42
references: 20092276
references: J Toxicol Environ Health A. 2002 Dec 27;65(24):2131-44
references: 12515591
references: Toxicol Sci. 2000 Mar;54(1):110-20
references: 10746938
references: Am J Pathol. 2007 Jan;170(1):1-15
references: 17200177
references: Tohoku J Exp Med. 2002 Jan;196(1):23-32
references: 12498323
references: Bull Environ Contam Toxicol. 2004 Jun;72(6):1091-7
references: 15362434
references: Int J Med Sci. 2014 Mar 21;11(5):488-93
references: 24688313
references: Toxicology. 2006 Mar 1;220(1):1-12
references: 16436312
references: Ren Fail. 1999 May-Jul;21(3-4):251-62
references: 10416202
references: Nat Rev Drug Discov. 2004 Jan;3(1):27-41
references: 14708019
references: Mol Cell Biochem. 2001 Jun;222(1-2):141-7
references: 11678596
references: Lancet. 1990 Sep 22;336(8717):699-702
references: 1975890
references: Toxicol In Vitro. 2009 Jun;23(4):569-73
references: 19490851
references: Carcinogenesis. 2011 Oct;32(10):1450-8
references: 21771726
references: Occup Environ Med. 2004 Feb;61(2):108-16
references: 14739376
references: Scand J Work Environ Health. 1998;24 Suppl 1:1-51
references: 9569444
references: Toxicol Lett. 2008 Jun 10;179(1):43-7
references: 18482805
references: Breast Cancer Res Treat. 2011 Jan;125(2):511-7
references: 20607602
references: Mol Cell Biochem. 2013 Mar;375(1-2):23-30
references: 23291979
references: J Inflamm (Lond). 2009 Jun 12;6:19
references: 19523218
references: Cancer Lett. 2009 Nov 1;284(2):122-30
references: 19303207
references: Lancet. 1999 Apr 3;353(9159):1140-4
references: 10209978
references: Tohoku J Exp Med. 2005 Mar;205(3):247-61
references: 15718817
references: Aging Clin Exp Res. 2012 Oct;24(5):530-6
references: 22732472
references: J Immunol. 2010 Dec 15;185(12):7435-42
references: 21068409
references: Arch Toxicol. 2002 Aug;76(8):449-51
references: 12185412
references: Met Ions Life Sci. 2013;11:491-507
references: 23430782
references: PLoS One. 2012;7(11):e50837
references: 23226399
references: Biometals. 2004 Oct;17(5):493-8
references: 15688852
references: Int Arch Occup Environ Health. 1987;59(1):21-30
references: 3793241
references: Toxicol In Vitro. 2015 Feb;29(1):242-50
references: 25448810
references: Toxicology. 2001 Mar 7;160(1-3):65-70
references: 11246125
references: Biometals. 2004 Oct;17(5):581-7
references: 15688869
references: Environ Health Perspect. 2010 Jun;118(6):790-5
references: 20064768
references: Pigment Cell Melanoma Res. 2013 Mar;26(2):193-204
references: 23176534
references: Am J Pathol. 2000 Feb;156(2):361-81
references: 10666364
references: Circulation. 2004 Jun 29;109(25):3196-201
references: 15184277
references: Melanoma Res. 2014 Oct;24(5):480-7
references: 25026000
references: J Toxicol Environ Health B Crit Rev. 2003 May-Jun;6(3):227-55
references: 12746140
references: Gastroenterology. 2005 Nov;129(5):1602-15
references: 16285959
references: Toxicol Sci. 2002 May;67(1):11-6
references: 11961211
references: J Natl Cancer Inst. 2006 Jun 21;98(12):869-73
references: 16788160
references: Cancer Res. 2008 Aug 1;68(15):6435-41
references: 18676869
references: Cell Death Differ. 1996 Jan;3(1):63-70
references: 17180056
references: Exp Cell Res. 2003 Jun 10;286(2):355-65
references: 12749863
references: Toxicology. 1985 Oct;37(1-2):117-25
references: 4060163
references: Bull Environ Contam Toxicol. 2006 Jan;76(1):8-15
references: 16404655
references: Mol Endocrinol. 2010 May;24(5):981-92
references: 20219890
references: Science. 2007 Dec 21;318(5858):1931-4
references: 18048652
references: J Biochem. 1996 Apr;119(4):817-22
references: 8743587
references: Int J Cancer. 2009 Aug 1;125(3):723-9
references: 19437537
references: Nanotoxicology. 2015 May;9(3):336-43
references: 24983898
references: Tumori. 2014 Jan-Feb;100(1):e4-7
references: 24675509
references: Int J Oncol. 2013 Dec;43(6):2046-56
references: 24064676
references: Free Radic Biol Med. 2014 Jun;71:1-15
references: 24642088
references: Cancer Res. 1988 Aug 15;48(16):4656-63
references: 3396014
references: Infect Immun. 2014 Dec;82(12):5013-22
references: 25225249
references: Eur J Immunol. 2012 Oct;42(10):2632-43
references: 22777843
references: Biometals. 2002 Dec;15(4):397-410
references: 12405535
references: Br J Dermatol. 2003 Sep;149(3):535-41
references: 14510986
references: Science. 2001 Aug 10;293(5532):1074-80
references: 11498575
references: Histopathology. 1998 Apr;32(4):340-7
references: 9602331
references: Mutat Res. 2003 Dec 10;533(1-2):107-20
references: 14643415
references: Cell. 2007 Feb 23;128(4):669-81
references: 17320505
references: J Clin Pathol. 2014 Jun;67(6):520-8
references: 24607493
references: Br J Dermatol. 2010 May;162(5):1093-7
references: 19845668
references: J Toxicol Environ Health A. 1998 May 22;54(2):159-68
references: 9652551
references: Lab Anim Sci. 1996 Oct;46(5):549-54
references: 8905589
references: PLoS One. 2013 Nov 13;8(11):e79781
references: 24236158
references: J Trace Elem Med Biol. 2005;19(1):69-73
references: 16240675
references: J Mol Med (Berl). 2001 Aug;79(8):428-36
references: 11511973
references: J Natl Cancer Inst. 1983 Feb;70(2):367-73
references: 6571943
references: Occup Environ Med. 2000 Oct;57(10):668-72
references: 10984338
references: Nat Rev Cancer. 2003 Jun;3(6):411-21
references: 12778131
references: Fundam Appl Toxicol. 1992 Jul;19(1):1-5
references: 1397789
references: Cancer. 1976 Apr;37(4):1782-7
references: 769938
references: Food Chem Toxicol. 2002 Aug;40(8):1179-84
references: 12067581
references: Toxicol Lett. 2003 Jan 31;137(1-2):65-83
references: 12505433
references: Cell Death Differ. 2007 Aug;14 (8):1467-74
references: 17464326
references: Int Immunopharmacol. 2014 Aug;21(2):439-46
references: 24946096
references: Toxicol Lett. 2002 Feb 28;127(1-3):47-54
references: 12052640
references: Pigment Cell Melanoma Res. 2014 Jul;27(4):590-600
references: 24495407
references: Int J Oncol. 2010 Oct;37(4):1031-41
references: 20811726
references: Cancer Invest. 1996;14(5):455-65
references: 8816861
references: Toxicology. 1995 Apr 12;98(1-3):1-13
references: 7740538
references: Int Arch Occup Environ Health. 2003 Apr;76(3):186-96
references: 12690493
references: Toxicol Appl Pharmacol. 1984 Sep 30;75(3):539-46
references: 6474481
references: Arch Environ Contam Toxicol. 1992 Jul;23(1):125-36
references: 1637191
references: ISRN Dermatol. 2014 Jan 22;2014:348417
references: 24587914
references: Nature. 1997 Jul 31;388(6641):482-8
references: 9242408
references: Toxicology. 2006 Mar 1;220(1):26-36
references: 16413650
references: Nat Cell Biol. 2010 Mar;12(3):235-46
references: 20173741
references: Environ Health Perspect. 2002 Jul;110(7):699-702
references: 12117647
references: Nat Med. 2003 Aug;9(8):1081-4
references: 12858169
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D152-7
references: 21037258
references: Toxicol Appl Pharmacol. 2005 Sep 1;207(2):179-86
references: 16102569
references: Curr Eye Res. 2013 Mar;38(3):335-41
references: 23216133
references: Arch Environ Health. 1993 May-Jun;48(3):157-63
references: 8333785
references: Biometals. 2004 Oct;17(5):555-8
references: 15688863
references: Cell Death Differ. 1996 Jan;3(1):57-62
references: 17180055
references: Biochem Biophys Res Commun. 2013 Nov 29;441(4):743-50
references: 24211571
references: Infect Immun. 2014 Nov;82(11):4508-17
references: 25114117