Abstract
Along with playing an important role in circadian rhythm, melatonin is thought to play a significant role in preventing cells from damage, as well as in the inhibition of growth and in triggering apoptosis in malignant cells. Its relationship with circadian rhythms, energetic homeostasis, diet, and metabolism, is fundamental to achieve a better comprehension of how melatonin has been considered a chemopreventive molecule, though very few papers dealing with this issue. In this article, we tried to review the most recent evidence regarding the protective as well as the antitumoral mechanisms of melatonin, as related to diet and metabolic balance. From different studies, it was evident that an intracellular antioxidant defense mechanism is activated by upregulating an antioxidant gene battery in the presence of high-dose melatonin in malignant cells. Like other broad-spectrum antioxidant molecules, melatonin plays a vital role in killing tumor cells, preventing metastasis, and simultaneously keeping normal cells protected from oxidative stress and other types of tissue damage.
Keywords: Melatonin, antioxidant, apoptosis, breast cancer, metastasis, oxidative stress.
[http://dx.doi.org/10.1016/j.yfrne.2004.08.001] [PMID: 15589268]
[http://dx.doi.org/10.1007/978-3-642-58932-4_1] [PMID: 9670565]
[PMID: 26313381]
[http://dx.doi.org/10.1016/j.jphysparis.2011.07.001] [PMID: 21914478]
[http://dx.doi.org/10.1097/WNR.0000000000001002] [PMID: 29528974]
[http://dx.doi.org/10.1212/CON.0000000000000499]
[http://dx.doi.org/10.1111/bph.14116] [PMID: 29318587]
[http://dx.doi.org/10.1111/1440-1681.12942] [PMID: 29603319]
[http://dx.doi.org/10.1111/j.1742-1241.2006.01191.x] [PMID: 17298593]
[http://dx.doi.org/10.1155/2017/1835195] [PMID: 29104591]
[http://dx.doi.org/10.1111/jpi.12085] [PMID: 24006943]
[http://dx.doi.org/10.1016/j.biopha.2016.12.119] [PMID: 28063410]
[http://dx.doi.org/10.1371/journal.pone.0150407] [PMID: 26934679]
[http://dx.doi.org/10.2174/1871520616666160923093229] [PMID: 27671309]
[http://dx.doi.org/10.1111/j.1600-079X.2009.00721.x] [PMID: 19925580]
[http://dx.doi.org/10.1007/s00232-010-9230-0] [PMID: 20130848]
[http://dx.doi.org/10.1111/j.1600-079X.2011.00876.x] [PMID: 21470303]
[http://dx.doi.org/10.1016/j.fertnstert.2011.08.013] [PMID: 21890129]
[http://dx.doi.org/10.1111/j.1600-079X.2011.00917.x] [PMID: 21812816]
[http://dx.doi.org/10.1016/j.mrfmmm.2012.08.006] [PMID: 22982225]
[http://dx.doi.org/10.1111/j.1600-079X.2012.00984.x] [PMID: 23050266]
[http://dx.doi.org/10.1002/cbin.10030] [PMID: 23364875]
[http://dx.doi.org/10.1007/s12640-012-9337-4] [PMID: 22739839]
[http://dx.doi.org/10.1002/jcb.24582] [PMID: 23824714]
[http://dx.doi.org/10.1111/jpi.12070] [PMID: 23796350]
[http://dx.doi.org/10.1016/j.phrs.2018.01.022] [PMID: 29408249]
[http://dx.doi.org/10.1111/jpi.12463] [PMID: 29247550]
[http://dx.doi.org/10.3402/mehd.v23i0.14787] [PMID: 23990836]
[http://dx.doi.org/10.1517/13543784.2012.681045] [PMID: 22500582]
[http://dx.doi.org/10.2174/187221412800604581] [PMID: 22369716]
[http://dx.doi.org/10.1111/jpi.12007] [PMID: 23013414]
[http://dx.doi.org/10.1159/000343338] [PMID: 23235525]
[PMID: 22753734]
[http://dx.doi.org/10.4046/trd.2012.73.6.312] [PMID: 23319993]
[http://dx.doi.org/10.1007/s10549-012-1953-4] [PMID: 22237979]
[http://dx.doi.org/10.1016/j.mce.2011.08.025] [PMID: 21889572]
[http://dx.doi.org/10.1002/mc.20832] [PMID: 21809392]
[http://dx.doi.org/10.1111/j.1600-079X.2012.00975.x] [PMID: 22289049]
[http://dx.doi.org/10.2174/092986712801661013] [PMID: 22612707]
[http://dx.doi.org/10.1111/j.1600-079X.2012.00974.x] [PMID: 22288984]
[http://dx.doi.org/10.1111/jpi.12035] [PMID: 23330808]
[http://dx.doi.org/10.1111/j.1600-079X.2012.00973.x] [PMID: 22335196]
[http://dx.doi.org/10.1111/j.1600-079X.2011.00946.x] [PMID: 22225575]
[http://dx.doi.org/10.3390/ijms14023901] [PMID: 23434670]
[http://dx.doi.org/10.1111/jpi.12032] [PMID: 23330677]
[http://dx.doi.org/10.1007/s10549-013-2487-0] [PMID: 23539297]
[http://dx.doi.org/10.1111/jpi.12264] [PMID: 26201382]
[http://dx.doi.org/10.1007/s00018-012-1161-8] [PMID: 23007844]
[http://dx.doi.org/10.3390/ijms14046597] [PMID: 23528889]
[http://dx.doi.org/10.1016/j.biopha.2012.10.005] [PMID: 23245210]
[http://dx.doi.org/10.1002/ar.22689] [PMID: 23564716]
[http://dx.doi.org/10.3109/10520295.2013.769633] [PMID: 23477595]
[http://dx.doi.org/10.3390/molecules23030518] [PMID: 29495398]
[http://dx.doi.org/10.2174/187152410793429683] [PMID: 20868358]
[http://dx.doi.org/10.1016/j.neures.2009.10.015] [PMID: 19914309]
[http://dx.doi.org/10.1111/jpi.12018] [PMID: 23110400]
[http://dx.doi.org/10.1111/jpi.12341] [PMID: 27121240]
[http://dx.doi.org/10.1002/jcp.27372] [PMID: 30229898]
[http://dx.doi.org/10.3390/ijms18040843] [PMID: 28420185]
[http://dx.doi.org/10.1089/ars.2013.5185] [PMID: 23373855]
[http://dx.doi.org/10.1111/jpi.12270] [PMID: 26292662]
[PMID: 29312489]
[http://dx.doi.org/10.1038/s41598-017-16940-y] [PMID: 29213108]
[http://dx.doi.org/10.1097/FBP.0000000000000384] [PMID: 29543650]
[http://dx.doi.org/10.3390/nu9040367] [PMID: 28387721]
[http://dx.doi.org/10.3390/ijms18040673] [PMID: 28333073]
[http://dx.doi.org/10.18632/oncotarget.16379] [PMID: 28415828]
[http://dx.doi.org/10.1016/j.bbrc.2018.02.010] [PMID: 29408377]
[http://dx.doi.org/10.1385/ENDO:27:2:101] [PMID: 16217123]
[http://dx.doi.org/10.1146/annurev-pharmtox-010814-124742] [PMID: 26514204]
[http://dx.doi.org/10.3390/ijms18061142] [PMID: 28587149]
[http://dx.doi.org/10.1002/(SICI)1097-0169(200005)46:1<28:AID-CM4>3.0.CO;2-5] [PMID: 10842331]
Joghataei, M.T. Melatonin regulates neuroinflammation ischemic stroke damage through interactions with microglia in reperfusion phase. Brain Res., 2019, 1723146401
[http://dx.doi.org/10.1016/j.brainres.2019.146401] [PMID: 31445031]
[http://dx.doi.org/10.1111/jpi.12467] [PMID: 29338098]
[http://dx.doi.org/10.1111/jpi.12373] [PMID: 27736013]
[http://dx.doi.org/10.1111/j.1600-079X.2010.00823.x] [PMID: 21062352]
[http://dx.doi.org/10.1096/fj.09-129148] [PMID: 19439501]
[http://dx.doi.org/10.1111/j.1600-079X.2009.00729.x] [PMID: 20025641]
[http://dx.doi.org/10.1074/jbc.M807869200] [PMID: 19075016]
[http://dx.doi.org/10.1210/me.2014-1293] [PMID: 25695910]
[http://dx.doi.org/10.1371/journal.pone.0106332] [PMID: 25184316]
[http://dx.doi.org/10.1111/jpi.12133] [PMID: 24650016]
[http://dx.doi.org/10.1096/fj.12-224691] [PMID: 23620527]
[http://dx.doi.org/10.1111/j.1600-079X.2006.00407.x] [PMID: 17198536]
[http://dx.doi.org/10.1023/A:1010968611716] [PMID: 11506187]
[http://dx.doi.org/10.3390/molecules23020336] [PMID: 29415446]
[http://dx.doi.org/10.18632/oncotarget.20525] [PMID: 29212174]
[http://dx.doi.org/10.1111/jpi.12620] [PMID: 31710386]
[http://dx.doi.org/10.1016/j.critrevonc.2017.12.018] [PMID: 29458781]
[http://dx.doi.org/10.2174/1871520617666171121120223] [PMID: 29173185]
[http://dx.doi.org/10.3390/ijms14048638] [PMID: 23609496]
[PMID: 16729718]
[http://dx.doi.org/10.1111/jpi.12442] [PMID: 28793364]
[http://dx.doi.org/10.23937/2378-3419/2/4/1024] [PMID: 26027592]
[http://dx.doi.org/10.1002/ar.21361] [PMID: 21416626]
[http://dx.doi.org/10.1016/j.fct.2017.10.039] [PMID: 29079495]
[http://dx.doi.org/10.1016/j.clinthera.2017.03.021] [PMID: 28438353]
[http://dx.doi.org/10.4062/biomolther.2017.071] [PMID: 28655071]
[http://dx.doi.org/10.3390/ijms18081694] [PMID: 28771183]
[http://dx.doi.org/10.1111/jpi.12393] [PMID: 28118492]
[http://dx.doi.org/10.1155/2016/2594703] [PMID: 27493704]
[http://dx.doi.org/10.4103/1735-5362.223801] [PMID: 29606970]
[http://dx.doi.org/10.1111/j.1600-079X.2006.00315.x] [PMID: 16635015]
[http://dx.doi.org/10.1074/jbc.M403140200] [PMID: 15229223]
[http://dx.doi.org/10.21873/anticanres.12437] [PMID: 29599315]
[http://dx.doi.org/10.3390/ijms18010165] [PMID: 28098843]
[http://dx.doi.org/10.1016/j.redox.2018.02.025] [PMID: 29525603]
[http://dx.doi.org/10.3892/or.2017.5446] [PMID: 28259965]
[http://dx.doi.org/10.2174/187152810793358741] [PMID: 20887269]
[http://dx.doi.org/10.1111/jpi.12380] [PMID: 27865009]
[http://dx.doi.org/10.18632/oncotarget.6407] [PMID: 26672764]
[http://dx.doi.org/10.1038/cddis.2016.330] [PMID: 27787516]
[http://dx.doi.org/10.1111/jpi.12365] [PMID: 27600920]
[http://dx.doi.org/10.18632/oncotarget.8009] [PMID: 26980735]
[http://dx.doi.org/10.1111/jpi.12308] [PMID: 26732239]
[http://dx.doi.org/10.7314/APJCP.2015.16.14.5835] [PMID: 26320459]
[http://dx.doi.org/10.1006/bbrc.1995.1952] [PMID: 7612003]
[http://dx.doi.org/10.1080/01635581.2015.1085582] [PMID: 26473998]
[http://dx.doi.org/10.1096/fasebj.13.1.69] [PMID: 9872931]
[http://dx.doi.org/10.1097/CEJ.0000000000000195] [PMID: 26340057]
[http://dx.doi.org/10.1016/j.phrs.2012.01.003] [PMID: 22311380]
[http://dx.doi.org/10.1017/S1462399409000982] [PMID: 19193248]
[http://dx.doi.org/10.1111/jpi.12119] [PMID: 24484372]
[http://dx.doi.org/10.1002/pros.20155] [PMID: 15378522]
[http://dx.doi.org/10.3390/cancers11111712] [PMID: 31684096]
[http://dx.doi.org/10.1371/journal.pone.0146643] [PMID: 26751389]
[http://dx.doi.org/10.1371/journal.pone.0099943] [PMID: 25000190]
[http://dx.doi.org/10.3390/ijms140610979] [PMID: 23708099]
[PMID: 26770154]
[http://dx.doi.org/10.1006/bbrc.1994.1401] [PMID: 7908519]
[http://dx.doi.org/10.1016/0098-2997(94)90033-7] [PMID: 7752835]
[PMID: 10893182]
[http://dx.doi.org/10.1016/S0891-5849(99)00111-2] [PMID: 10490284]
[http://dx.doi.org/10.1177/030089160308900416] [PMID: 14606649]
[http://dx.doi.org/10.1016/S0304-4165(03)00048-5] [PMID: 12667613]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0851] [PMID: 18094428]
[http://dx.doi.org/10.1016/j.ejphar.2009.10.009] [PMID: 19836383]
[http://dx.doi.org/10.1080/08910600701343286]
[http://dx.doi.org/10.1016/j.semcancer.2017.04.005] [PMID: 28445781]
[http://dx.doi.org/10.1111/j.1600-079X.2009.00663.x] [PMID: 19220725]
[http://dx.doi.org/10.12659/MSM.897114] [PMID: 26861593]
[http://dx.doi.org/10.1111/jpi.12176] [PMID: 25230823]
[http://dx.doi.org/10.1177/1534735405276191] [PMID: 15911925]
[http://dx.doi.org/10.1016/j.lfs.2016.01.026] [PMID: 26784848]
[http://dx.doi.org/10.1111/jpi.12310] [PMID: 26732476]
[http://dx.doi.org/10.1016/j.biotechadv.2015.12.014] [PMID: 26740171]
[http://dx.doi.org/10.1016/j.phrs.2015.12.027] [PMID: 26731017]
[http://dx.doi.org/10.1016/j.redox.2013.12.022] [PMID: 24494192]
[http://dx.doi.org/10.2174/0929867322666150619104143] [PMID: 26087763]
[http://dx.doi.org/10.1016/j.clnu.2013.03.008] [PMID: 23582951]
[http://dx.doi.org/10.1007/978-1-4615-0135-0_63] [PMID: 15206773]
[http://dx.doi.org/10.1111/jpi.12304] [PMID: 26681257]
[http://dx.doi.org/10.1177/0960327114559993] [PMID: 26286521]
[http://dx.doi.org/10.1016/j.brainres.2010.03.033] [PMID: 20303338]
[http://dx.doi.org/10.3390/nu8020078] [PMID: 26861391]
[http://dx.doi.org/10.1530/ERC-15-0030] [PMID: 25876649]
[http://dx.doi.org/10.1006/bbrc.1998.9370] [PMID: 9784392]
[http://dx.doi.org/10.1186/s12967-015-0454-8] [PMID: 25889845]
[http://dx.doi.org/10.1111/j.1600-079X.2008.00605.x] [PMID: 18507712]
[http://dx.doi.org/10.1111/jpi.12062] [PMID: 23725013]
[http://dx.doi.org/10.3109/10715762.2011.623700] [PMID: 21923620]
[http://dx.doi.org/10.1111/j.1742-7843.2010.00619.x] [PMID: 20649556]
[http://dx.doi.org/10.1111/jpi.12358] [PMID: 27484637]
[http://dx.doi.org/10.3892/or.2015.3738] [PMID: 25606968]
[http://dx.doi.org/10.3109/10799893.2012.737002] [PMID: 23194197]
[http://dx.doi.org/10.1097/CEJ.0000000000000030] [PMID: 24858716]
[http://dx.doi.org/10.1093/aje/kwt302] [PMID: 24418683]
[http://dx.doi.org/10.1136/oem.2009.047092] [PMID: 19819854]
[http://dx.doi.org/10.1111/j.1600-079X.2007.00451.x] [PMID: 17614829]
[PMID: 12589398]
[http://dx.doi.org/10.18632/oncotarget.7936] [PMID: 26958939]
[http://dx.doi.org/10.1016/j.ejca.2016.05.026] [PMID: 27391920]
[http://dx.doi.org/10.1038/ijo.2017.218] [PMID: 28883539]
[http://dx.doi.org/10.1038/ijo.2017.285] [PMID: 29151594]
[http://dx.doi.org/10.1186/s13048-019-0502-8] [PMID: 30914056]
[http://dx.doi.org/10.1186/s13287-015-0249-0] [PMID: 26718286]
[http://dx.doi.org/10.1042/CS20180945] [PMID: 30808718]
[http://dx.doi.org/10.1111/j.1600-079X.2011.00875.x] [PMID: 21470302]
[http://dx.doi.org/10.1159/000110635] [PMID: 18073503]
[http://dx.doi.org/10.1007/s00280-012-1886-y] [PMID: 22610356]
[http://dx.doi.org/10.1177/1534735411425484] [PMID: 22019490]
[http://dx.doi.org/10.1111/j.1600-079X.2005.00258.x] [PMID: 16207291]