{"id":1965,"date":"2020-05-05T16:57:58","date_gmt":"2020-05-05T14:57:58","guid":{"rendered":"https:\/\/www.newslab.sk\/protinadorove-ucinky-vitaminu-d\/"},"modified":"2020-05-05T17:00:51","modified_gmt":"2020-05-05T15:00:51","slug":"anti-tumour-effects-of-vitamin-d","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/anti-tumour-effects-of-vitamin-d\/","title":{"rendered":"Anti-tumour effects of vitamin D"},"content":{"rendered":"<p><span style=\"color: #ff0000;\"><strong>*<\/strong><strong>All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/strong><\/span><\/p>\n<p>&nbsp;<\/p>\n<p><strong>\u00davod<\/strong><\/p>\n<p>V s\u00fa\u010dasnosti sa na vitam\u00edn D nahliada ako na steroidn\u00fd horm\u00f3n rozpustn\u00fd v tukoch, ktor\u00e9ho gen\u00f3mov\u00e9 \u00fa\u010dinky s\u00fa sprostredkovan\u00e9 po naviazan\u00ed na \u0161pecifick\u00fd receptor. K potvrden\u00fdm \u00fa\u010dinkom vitam\u00ednu D okrem uchovania zdrav\u00fdch kost\u00ed (tzv. klasick\u00e9 \u00fa\u010dinky) rad\u00edme tzv. neklasick\u00e9, nonkalcemick\u00e9 \u00fa\u010dinky. Tie sa aktu\u00e1lne sleduj\u00fa pri autoimunitn\u00fdch a kardiovaskul\u00e1rnych ochoreniach, precitlivenosti na infekcie, pri vzniku n\u00e1dorov\u00fdch ochoren\u00ed, ale aj v s\u00favislosti s priebehom fyziologick\u00e9ho starnutia. Vzh\u013eadom na \u0161irok\u00fd rozsah s\u00fa\u010dasn\u00fdch poznatkov sa v tomto pr\u00edspevku budeme podrobnej\u0161ie venova\u0165 vz\u0165ahu vitam\u00ednu D k vzniku a progresii n\u00e1dorov\u00fdch ochoren\u00ed, kde sa opakovane potvrdili jeho v\u00fdznamn\u00e9 antikancerog\u00e9nne vlastnosti. K t\u00fdm najd\u00f4le\u017eitej\u0161\u00edm patr\u00ed indukcia zastavenia bunkov\u00e9ho cyklu, stimul\u00e1cia apopt\u00f3zy a inhib\u00edcia angiogen\u00e9zy(1), ale uplat\u0148uje sa aj pri z\u00e1paloch asociovan\u00fdch s n\u00e1dorov\u00fdm ochoren\u00edm, reparat\u00edvnych procesoch DNA a metast\u00e1zovan\u00ed. Preh\u013ead mechanizmov \u00fa\u010dinku vitam\u00ednu D s antikancerog\u00e9nnym efektom sumarizuje <strong><em>tabu\u013eka 1<\/em><\/strong>.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Indukcia<\/strong> <strong>zastavenia<\/strong> <strong>bunkov\u00e9ho<\/strong> <strong>cyklu<\/strong> <strong>a stimul\u00e1cia apopt\u00f3zy<\/strong><\/p>\n<p>Proliferuj\u00faca bunka prech\u00e1dza vysoko usporiadan\u00fdmi f\u00e1zami G1, S, G2 a M v sekvencii, z ktor\u00fdch kritick\u00e9 s\u00fa S (f\u00e1za synt\u00e9zy DNA) a M (f\u00e1za mit\u00f3zy). Vstup do nich (za\u010diatok S f\u00e1zy a M f\u00e1zy) je pr\u00edsne regulovan\u00fd, \u010do vedie k vzniku dvoch \u201ekontroln\u00fdch bodov\u201c v cykle. Po\u0161kodenie DNA z akejko\u013evek pr\u00ed\u010diny m\u00f4\u017ee zastavi\u0165 bunkov\u00fd cyklus v hociktorej z t\u00fdchto f\u00e1z a presn\u00fd priebeh cyklu v nich ur\u010duje genetick\u00fa stabilitu bunky. V\u0161eobecne najv\u00e4\u010d\u0161\u00ed antiprolifera\u010dn\u00fd \u00fa\u010dinok m\u00e1 indukcia zastavenia bunkov\u00e9ho cyklu zalo\u017een\u00e1 na blok\u00e1de G1 f\u00e1zy (26), ktor\u00fa mo\u017eno dosiahnu\u0165 navoden\u00edm zv\u00fd\u0161enej tvorby prote\u00ednov p21 a p27. Pri akt\u00edvnej forme vitam\u00ednu D 1,25-(OH)2D3 sa preuk\u00e1zala schopnos\u0165 zastavi\u0165 bunkov\u00fd cyklus v n\u00e1dorov\u00fdch bunkov\u00fdch l\u00edni\u00e1ch aj vo f\u00e1ze G2\/M(3). Vitam\u00edn D je schopn\u00fd navodi\u0165 apopt\u00f3zu n\u00e1dorov\u00fdch buniek u\u017e na g\u00e9novej \u00farovni prostredn\u00edctvom inhib\u00edcie zn\u00e1meho antiapoptotick\u00e9ho g\u00e9nu Bcl-2 (B-cell lymphoma 2)(4), indukciou proapoptotick\u00fdch g\u00e9nov, ako je DAP (Death-Associated Protein-3), CFKAR <em>(<\/em>caspase 8 apoptosis-related cysteine peptidase) a FADD (Fas-Associated protein with Death Domain)(5), a dok\u00e1\u017ee dokonca aktivova\u0165 proautofagick\u00fd g\u00e9n beclin-1(6). Okrem toho kalcitriol zvy\u0161uje aktivitu proapoptotick\u00fdch prote\u00ednov Bax a \u03bc-calpain(3,7-9). Schopnos\u0165 navodenia apopt\u00f3zy je jednozna\u010dne jednou z najd\u00f4le\u017eitej\u0161\u00edch funkci\u00ed prote\u00ednu p53, zn\u00e1meho hlavn\u00e9ho regul\u00e1tora apopt\u00f3zy a produktu tumor-supresorov\u00e9ho g\u00e9nu TP53. Pri viacer\u00fdch n\u00e1dorov\u00fdch bunkov\u00fdch l\u00edni\u00e1ch bolo zisten\u00e9, \u017ee mechanizmus indukcie apopt\u00f3zy prostredn\u00edctvom vitam\u00ednu D var\u00edruje v z\u00e1vislosti od typu bunky a m\u00f4\u017ee by\u0165 sprostredkovan\u00fd prote\u00ednom p53, ale aj bez jeho pr\u00edtomnosti(10,11).<\/p>\n<p>&nbsp;<\/p>\n<h3>Inhib\u00edcia angiogen\u00e9zy<\/h3>\n<p>Efekt vitam\u00ednu D na angiogen\u00e9zu bol prv\u00fdkr\u00e1t op\u00edsan\u00fd v roku 1990, ke\u010f sa zistilo, \u017ee 1,25-(OH)2D3 a jeho anal\u00f3g 22-oxo- 1,25-D3 inhibuje embryon\u00e1lnu angiogen\u00e9zu v choriovej membr\u00e1ne(12). Podpora angiogen\u00e9zy n\u00e1doru, jeho inv\u00e1zie a metast\u00e1zovania m\u00f4\u017ee by\u0165 d\u00f4sledkom aktiv\u00e1cie tzv. sp\u00edna\u010dov angiogen\u00e9zy, ktor\u00fdch aktiv\u00e1ciu kontroluje predov\u0161etk\u00fdm endoteli\u00e1lny rastov\u00fd faktor (Vascular Endothelial Growth Factor, VEGF)(13). Bolo preuk\u00e1zan\u00e9, \u017ee vitam\u00edn D dok\u00e1\u017ee zni\u017eova\u0165 expresiu VEGF v n\u00e1dorov\u00fdch bunk\u00e1ch a tie\u017e zni\u017euje odpove\u010f endoteli\u00e1lnych buniek na tento faktor(14). Z\u00e1konite je hypoxia v\u00fdrazn\u00fd induktor tvorby VEGF a po\u010das jej p\u00f4sobenia, za s\u00fa- \u010dasnej aplik\u00e1cie vitam\u00ednu D, doch\u00e1dzalo k signifikantn\u00e9mu zn\u00ed\u017eeniu tvorby VEGF(15).<\/p>\n<p>&nbsp;<\/p>\n<h3>Glykolytick\u00fd metabolizmus n\u00e1dorov\u00fdch buniek<\/h3>\n<p>Kalcitriol svojimi antikancerog\u00e9nnymi \u00fa\u010dinkami zasahuje aj do energetick\u00e9ho metabolizmu n\u00e1dorov\u00fdch buniek. Anaer\u00f3bny sp\u00f4sob spracovania gluk\u00f3zy preferovan\u00fd mal\u00edgne transformovan\u00fdmi bunkami je negat\u00edvne regulovan\u00fd akt\u00edvnymi formami vitam\u00ednu D. Santos a kol. (2017) vo svojej \u0161t\u00fadii na bunkov\u00fdch kult\u00farach z\u00edskan\u00fdch z karcin\u00f3mu prsn\u00edka zaznamenali pokles miery glykol\u00fdzy po podan\u00ed vitam\u00ednu D. Vitam\u00edn D dok\u00e1zal zn\u00ed\u017ei\u0165 expresiu membr\u00e1nov\u00fdch gluk\u00f3zov\u00fdch transport\u00e9rov GLUT1 a tak spomali\u0165 utiliz\u00e1ciu gluk\u00f3zy n\u00e1dorov\u00fdmi bunkami. Dok\u00e1zan\u00e1 bola aj supresia aktiv\u00e1cie mTOR (z angl. mammalian target of rapamycin), ktor\u00fd je s\u00fa\u010das\u0165ou sign\u00e1lnej dr\u00e1hy Warburgovho efektu \u2013 tzn. preferencie anaer\u00f3bnej glykol\u00fdzy n\u00e1dorov\u00fdmi bunkami. Santos a kol. (2017) dok\u00e1zali aj zn\u00ed\u017een\u00fa produkciu lakt\u00e1tu po lie\u010dbe vitam\u00ednom D <strong><em>(obr\u00e1zok 1)<\/em><\/strong>(16).<\/p>\n<h3>Z\u00e1pal asociovan\u00fd s n\u00e1dormi a vitam\u00edn D<\/h3>\n<p>Z\u00e1pal asociovan\u00fd s n\u00e1dormi je d\u00f4le\u017eitou s\u00fa\u010das\u0165ou viacer\u00fdch aspektov tumorogen\u00e9zy a v\u00fdvoja n\u00e1dorov\u00e9ho ochorenia. K potvrden\u00fdm \u00fa\u010dinkom vitam\u00ednu D patr\u00ed taktie\u017e schopnos\u0165 zni\u017eova\u0165 tvorbu proz\u00e1palov\u00fdch cytok\u00ednov aj ich biologick\u00fa aktivitu, \u010do predstavuje v\u00fdznamn\u00fd protiz\u00e1palov\u00fd efekt(18). Z\u00e1palov\u00e1 reakcia sprev\u00e1dzaj\u00faca rast n\u00e1doru je vo v\u0161eobecnosti charakterizovan\u00e1 pr\u00edtomnos\u0165ou z\u00e1palov\u00fdch buniek, medi\u00e1torov z\u00e1palovej reakcie, ako s\u00fa cytok\u00edny, chemok\u00edny, prostagland\u00edny a kysl\u00edkov\u00e9 radik\u00e1ly(19). Pr\u00e1ve aktivita VEGF v\u00fdznamne z\u00e1vis\u00ed aj od medi\u00e1torov z\u00e1palu. Schopnos\u0165ou zn\u00ed\u017ei\u0165 z\u00e1palov\u00fa reakciu m\u00f4\u017ee teda vitam\u00edn D prostredn\u00edctvom VEGF zasahova\u0165 aj do n\u00e1dorovej angiogen\u00e9zy. V literat\u00fare sa opisuje tie\u017e vznik n\u00e1dorov\u00fdch ochoren\u00ed v d\u00f4sledku chronick\u00e9ho z\u00e1palov\u00e9ho procesu. So vznikom n\u00e1dorov\u00fdch ochoren\u00ed, obzvl\u00e1\u0161\u0165 s procesom, ktor\u00fd vedie od z\u00e1palu ku kancerogen\u00e9ze, sa opakovane sp\u00e1ja skupina transkrip\u010dn\u00fdch faktorov zn\u00e1mych pod ozna\u010den\u00edm NF-\u03baB (Nuclear Factor Kappa B), ktor\u00e9 sa podie\u013eaj\u00fa na kon-trole transkripcie DNA, produkcie cytok\u00ednov a bunkov\u00e9ho pre\u017e\u00edvania(20). V porovnan\u00ed so zdrav\u00fdmi bunkami mali mnoh\u00e9 n\u00e1dorov\u00e9 bunky zv\u00fd\u0161en\u00e9 hladiny NF-\u03baB. Potvrdilo sa, \u017ee kalcitriol je schopn\u00fdblokova\u0165 aktiv\u00e1ciu NF-\u03baB(21) a t\u00e1to inhib\u00edcia sa jav\u00ed ako ve\u013emi s\u013eubn\u00e1 mo\u017enos\u0165 protin\u00e1dorovej lie\u010dby. Kalcitriol vykazuje protiz\u00e1palov\u00fa aktivitu vo viacer\u00fdch typoch mal\u00edgnych n\u00e1dorov. Zmenami expresie NF-\u03baB, jeho translok\u00e1cie do jadra a v\u00e4zby na \u0161pecifick\u00e9 sekvencie na DNA vitam\u00edn D zni\u017eoval expresie proz\u00e1palovo p\u00f4sobiaceho cytok\u00ednu IL-8 napr\u00edklad v bunk\u00e1ch karcin\u00f3mu prostaty D(21). Vitam\u00edn D men\u00ed expresiu NF-\u03baB p\u00f4soben\u00edm na IGFBP-3 (insuline-like growth factor binding protein), ktor\u00fd reguluje funkciu NF-\u03baB(22).<\/p>\n<p>Vitam\u00edn D v\u00fdznamne zasahuje aj do synt\u00e9zy a biologickej aktivity prostagland\u00ednov v zmysle ich inhib\u00edcie. Prostagland\u00edny podporuj\u00fa karcinogen\u00e9zu, pozit\u00edvnym sp\u00f4sobom indukuj\u00fa bunkov\u00fa prolifer\u00e1ciu, angiogen\u00e9zu a vpl\u00fdvaj\u00fa na rozvoj metast\u00e1z. Vitam\u00edn D vstupuje do ich metabolizmu a biologickej aktivity 3 z\u00e1kladn\u00fdmi mechanizmami: inhib\u00edciou enz\u00fdmu cyklooxygen\u00e1za 2 (COX-2), ktor\u00fd je k\u013e\u00fa\u010dov\u00fd v synt\u00e9ze prostagland\u00ednov upregul\u00e1ciou expresie enz\u00fdmu 15-hydroxyprostagland\u00edndehydrogen\u00e1za (15-PGHD), ktor\u00fd je zodpovedn\u00fd za degrad\u00e1ciu prostagland\u00ednov downregul\u00e1ciou expresie membr\u00e1nov\u00fdch prostagland\u00ednov\u00fdch receptorov, esenci\u00e1lnych pre bunkov\u00fa signaliz\u00e1ciu <strong><em>(obr\u00e1zok 2)<\/em><\/strong>(22)<\/p>\n<p>Krishan a Feldmann (2011)(22) rovnako uv\u00e1dzaj\u00fa, \u017ee d\u00f4le\u017eit\u00fdmi cie\u013eov\u00fdmi molekulami vitam\u00ednu D v procese z\u00e1palu s\u00fa aj MAP kin\u00e1zy. Napr\u00edklad expresia MAP kin\u00e1zy \u2013 fosfat\u00e1zy 5 (MKP5) je indukovan\u00e1 kalcitriolom a n\u00e1sledne inhibuje stresov\u00fd prote\u00edn p38, \u010do vedie k zn\u00ed\u017eeniu expresie proz\u00e1palov\u00fdch cytok\u00ednov, najm\u00e4 IL-6.<\/p>\n<p>&nbsp;<\/p>\n<h3>\u00daloha vitam\u00ednu D v prevencii n\u00e1dorovej invazivity a vzniku metast\u00e1z<\/h3>\n<p>Vznik metast\u00e1z je komplexn\u00fd proces zah\u0155\u0148aj\u00faci bunkov\u00fa adh\u00e9ziu, migr\u00e1ciu, inv\u00e1ziu, prolifer\u00e1ciu a angiogen\u00e9zu(21). Pre kancerogen\u00e9zu na molekulovej \u00farovni maj\u00fa ve\u013ek\u00fd v\u00fdznam sign\u00e1lne dr\u00e1hy v bunke. Poruchy v t\u00fdchto kask\u00e1dach \u2013 obvykle overexpresia alebo inhib\u00edcia ur\u010dit\u00e9ho medzi\u010dl\u00e1nku kask\u00e1dy \u2013 m\u00f4\u017eu v bunke vyvol\u00e1va\u0165 zmeny, ktor\u00e9 jej poskytn\u00fa prolifera\u010dn\u00e9 v\u00fdhody.<\/p>\n<p>\u00daloha vitam\u00ednu D v s\u00favislosti s n\u00e1dorovou invazivitou sa v s\u00fa\u010dasnosti podrobne \u0161tuduje pri kolorekt\u00e1lnom karcin\u00f3me. Pri tomto type n\u00e1doru sa a\u017e v 90 % objavuje porucha v prie- behu Wnt\/betakaten\u00ednovej sign\u00e1lnej dr\u00e1hy, a to na \u00farovni betakaten\u00ednu (prote\u00edn podie\u013eaj\u00faci sa na medzibunkovom ad- h\u00e9znom spojen\u00ed). Presun tohto prote\u00ednu z cytoplazmy do bunkovej membr\u00e1ny dok\u00e1\u017ee ovplyvni\u0165 hladina vitam\u00ednu D(23). Di\u00e1z a kol. (2010)(24) uv\u00e1dzaj\u00fa, \u017ee vitam\u00edn D je siln\u00fdm induktorom expresie cystat\u00ednu D, inhib\u00edtora cyste\u00ednov\u00fdch prote\u00e1z z kateps\u00ednovej rodiny. Cystat\u00edn D sa podie\u013ea na antikancerog\u00e9nnych \u00fa\u010dinkoch vitam\u00ednu D, taktie\u017e najm\u00e4 v pr\u00edpadoch kolorekt\u00e1lneho karcin\u00f3mu. Je zapojen\u00fd do procesov zni\u017euj\u00facich migra\u010dn\u00fa aktivitu buniek a potl\u00e1\u010da funkcie g\u00e9nov tzv. epiteli\u00e1lno-mezenchym\u00e1lneho prechodu. Pr\u00e1ve produkty t\u00fdchto g\u00e9nov s\u00fa schopn\u00e9 potl\u00e1\u010da\u0165 fyziologicky pr\u00edtomn\u00fa polaritu epitelov\u00fdch buniek, ktor\u00e1 je tie\u017e dan\u00e1 pr\u00edtomnos\u0165ou \u0161pecifick\u00fdch adhez\u00edvnych \u0161trukt\u00far.<\/p>\n<p>Vitam\u00edn D sa tie\u017e z\u00fa\u010dast\u0148uje na regul\u00e1cii matrixov\u00fdch metaloprote\u00e1z (MMPs) a \u0161pecifick\u00fdch tkanivov\u00fdch inhib\u00edtorov matrixov\u00fdch metaloprote\u00e1z (TIMPs). MMPs s\u00fa prote\u00e1zy dependentn\u00e9 od zinku, schopn\u00e9 degradova\u0165 zlo\u017eky extracelul\u00e1rneho matrixu a baz\u00e1lnej membr\u00e1ny. MMPs aj TIMPs b\u00fdvaj\u00fa \u010dasto dysfunk\u010dn\u00e9 pri mal\u00edgnych n\u00e1dorov\u00fdch ochoreniach a tieto dysfunk\u010dn\u00e9 zmeny prispievaj\u00fa k invazivite a potenci\u00e1lu zaklada\u0165 vzdialen\u00e9 metast\u00e1zy.<\/p>\n<p>Viacer\u00e9 \u0161t\u00fadie pouk\u00e1zali na skuto\u010dnos\u0165, \u017ee suplement\u00e1cia vitam\u00ednu D zni\u017euje expresiu metaloprote\u00e1zy 9 (MMP 9) a zvy\u0161uje expresiu TIMP 1 pri karcin\u00f3me prsn\u00edka a prostaty(24).<\/p>\n<p>&nbsp;<\/p>\n<h3>Z\u00e1ver<\/h3>\n<p>V s\u00fa\u010dasnosti je vitam\u00edn D pre svoje biologick\u00e9 vlastnosti pova\u017eovan\u00fd za horm\u00f3n a pre \u0161irok\u00e9 spektrum p\u00f4sobenia sa opr\u00e1vnene prirovn\u00e1va k horm\u00f3nom \u0161t\u00edtnej \u017e\u013eazy. Epidemiologick\u00e9 \u0161t\u00fadie nazna\u010duj\u00fa, \u017ee nedostatok vitam\u00ednu D by mohol zohr\u00e1va\u0165 d\u00f4le\u017eit\u00fa \u00falohu aj v etiol\u00f3gii r\u00f4znych typov n\u00e1dorov\u00fdch ochoren\u00ed u \u013eud\u00ed. Protin\u00e1dorov\u00e1 aktivita sa aktu\u00e1lne zara\u010fuje medzi jeho neklasick\u00e9 (nonkalcemick\u00e9) \u00fa\u010dinky a m\u00f4\u017ee by\u0165 sprostredkovan\u00e1 viacer\u00fdmi mechanizma- mi vr\u00e1tane inhib\u00edcie bunkovej prolifer\u00e1cie, indukcie apopt\u00f3zy, stimul\u00e1cie diferenci\u00e1cie, potla\u010denia inv\u00e1zie n\u00e1doru, metast\u00e1zy a angiogen\u00e9zy. Predklinick\u00fd v\u00fdskum nazna\u010duje, \u017ee akt\u00edvny metabolit vitam\u00ednu D (ev. jeho anal\u00f3g) by sa mohol uplatni\u0165 ako prevent\u00edvna a terapeutick\u00e1 protirakovinov\u00e1 l\u00e1tka.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>LITERAT\u00daRA<\/strong><\/p>\n<ol>\n<li>Holick Vitamin D deficiency. N Engl J Med 2007; 357: 266-281.<\/li>\n<li>Feldman D, Krishnan AV, Swami S, et The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 2014; 14(5): 342-357. doi: 10.1038\/nrc3691. Epub 2014 Apr 4.<\/li>\n<li>Jiang F, Li P, Fornace AJ Jr, et G2\/M arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer. J Biol Chem 2003; 278(48): 48030-48040.<\/li>\n<li>Blutt SE, McDonnell TJ, Polek TC, et Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of Bcl-2. Endocrinology 2000; 141: 10-17.<\/li>\n<li>Bikle Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 2014; 21: 319-329.<\/li>\n<li>H\u00f8yer-Hansen M, Bastholm L, Mathiasen IS, et Vitamin D analog EB1089 triggers dramatic lysosomal changes and Beclin 1-mediated autophagic cell death. Cell Death Differ 2005; 12: 1297-1309.<\/li>\n<li>James SY, Mackay AG, Colston KW. Effects of 1,25 dihydroxyvita- min D3 and its analogues on induction of apoptosis in breast cancer cells. Journal of Steroid Biochemistry and Molecular Biology 1996; 58(4): 395-401.<\/li>\n<li>Diaz GD, Paraskeva C, Thomas MG, et Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Research 2000; 60(8): 2304-2312.<\/li>\n<li>Kumagai T, Shih LY, Hughes SV, et 19-Nor-l,25(OH)2D2 (a novel, noncalcemic vitamin D analogue), combined with arsenic trioxide, has potent antitumor activity against myeloid leukemia. Cancer Research 2005; 65(6): 2488-2497.<\/li>\n<li>Fridman JS, Lowe Control of apoptosis by p53. Oncogene 2003; 22(56): 9030-40.<\/li>\n<li>Chakraborti Vitamin D as a promising anticancer agent. Indian J Pharmacol 2011; 43(2): 113-120.<\/li>\n<li>Oikawa T, et 1990. Inhibition of angiogenesis by vitamin D3 analogues. European Journal of Pharmacology 1990; 178(2), s. 247-250.<\/li>\n<li>Kundu JK, Surh Inflammation: gearing the journey to cancer. Mutat Res 2008; 659(1-2): 15-30.<\/li>\n<li>Mantell DJ, Owens PE, Bundred NJ, et 1 Alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circulation Research 2000; 87(3): 214-220.<\/li>\n<li>Ben-Shoshan M, \u00a0Amir \u00a0S, \u00a0Dang \u00a0DT, \u00a0et \u00a0 \u00a01\u03b1,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1\/vascular endothelial growth factor pathway in human cancer cells. Mol. Cancer Ther 2007; 6: 1433-1439.<\/li>\n<li>Santos JM, et 2017. Vitamin D3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells. J Nutr Bio- chem 2018; 53: s. 111-120.<\/li>\n<li>Gibas The Retrograde Signal: Dependency on Glucose Marks the Cancerous Phenotype. Austin J Nutr Metab 2017; 4(2): 1051.<\/li>\n<li>Moreno J, Krishnan AV, Swami S, et Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells. Cancer Res 2005; 65(17): 7917-7925.<\/li>\n<li>Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflamma- Nature 2008; 454(7203): 436-444.<\/li>\n<li>Hoesel B, Schmid The complexity of NF-\u03baB signaling in inflamma- tion and cancer. Mol Cancer 2013; 12: 86.<\/li>\n<li>MA Y, et al. 2016. Mechanistic Insights of Vitamin D Anticancer Ef- fects. Vitamins and Hormones 2016; 100: 395-431.<\/li>\n<li>Krishan AV, Feldman D. Mechanisms of the Anti-Cancer and Anti-Inflammatory Actions of Vitamin Annu. Rev. Pharmacol. Toxicol 2011; 51: s. 311-336.<\/li>\n<li>Piccoto G, et 2012. Molecular Aspects of Vitamin D Anticancer Activity. Cancer Investigation 2012; 30: s.604\u2013614<\/li>\n<li>Di\u00e1z S \u00c1, et Proteases, protease inhibitors and cancer. Cell Cycle 2010; 9(1): s. 32-37.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper. &nbsp; \u00davod V s\u00fa\u010dasnosti sa na vitam\u00edn D nahliada ako na steroidn\u00fd horm\u00f3n rozpustn\u00fd v tukoch, ktor\u00e9ho gen\u00f3mov\u00e9 \u00fa\u010dinky s\u00fa sprostredkovan\u00e9 po naviazan\u00ed na \u0161pecifick\u00fd receptor. K potvrden\u00fdm \u00fa\u010dinkom vitam\u00ednu<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[289],"tags":[1437,1436,1433,1434,1435],"class_list":["post-1965","post","type-post","status-publish","format-standard","hentry","category-biochemistry","tag-antitumor-effects","tag-carcinogenesis","tag-kancerogeneza-en","tag-protinadorove-ucinky-en","tag-vitamin-d-en","typ_clanku-review-article"],"acf":{"abstrakt":"<p>Vitamin D deficiency was initially discovered as the cause of rickets due to insufficient exposure to sunlight or intake of vitamin D-rich foods. In addition to its role in calcium and bone homeostasis, vitamin D participates in the regulation of many other cellular functions. The vitamin D receptor (VDR) is almost universally expressed in nuclear cells. Thus, the spectrum of vitamin D endocrine activity is much broader than calcium\/bone homeostasis, and the vitamin D-VDR system resembles that of other nuclear receptor ligands, such as thyroid hormones, in this respect.<\/p>\n<p>Given the full range of current knowledge about vitamin D, we discuss in more detail the relationship of vitamin D to cancer development and progression, where its significant anticancerogenic properties have been repeatedly confirmed. The most important are induction of cell cycle arrest, stimulation of apoptosis and inhibition of angiogenesis. Still, it is also applied to inflammation associated with cancer and reparative DNA processes and metastasis.<\/p>\n<p><strong>Keywords: <\/strong>vitamin D, carcinogenesis, antitumor effects<\/p>\n","casopis":[{"ID":1893,"post_author":"7","post_date":"2020-05-05 11:32:54","post_date_gmt":"2020-05-05 09:32:54","post_content":"<ul>\r\n \t<li>Identification of metabolic pathways in pathogenesis of diabetic retinopathy using exome sequencing \u2013 a pilot study<\/li>\r\n \t<li>Anti-tumour effects of vitamin D<\/li>\r\n \t<li>Molecular detection methods of mutations in the kinase domain of fusion gene bcr-abl1 in patients with chronic myelocyte leukemia<\/li>\r\n \t<li>The case report of toxoplasmic meningoencephalitis with fatal outcome in HIV patient<\/li>\r\n \t<li>Carcinosarcoma-like endometrioid carcinoma of the uterus: case report of rare non-high-grade tumor<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-4","to_ping":"","pinged":"","post_modified":"2020-05-05 15:13:41","post_modified_gmt":"2020-05-05 13:13:41","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/?post_type=casopis&#038;p=1893","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"","upload_clanok":{"ID":1963,"id":1963,"title":"NEWSLAB_1-2020_Boler\u00e1zska","filename":"NEWSLAB_1-2020_Boler\u00e1zska.pdf","filesize":283769,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2020\/05\/NEWSLAB_1-2020_Boler\u00e1zska.pdf","link":"https:\/\/www.newslab.sk\/en\/anti-tumour-effects-of-vitamin-d\/newslab_1-2020_bolerazska-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab_1-2020_bolerazska-2","status":"inherit","uploaded_to":1965,"date":"2020-05-05 14:49:48","modified":"2020-05-05 14:49:48","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1965","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1965"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1965\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1965"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1965"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1965"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}