Uloga polifenola u epigenetskoj regulaciji tumora

undergraduate thesis

• Title (english): The role of polyphenols in the epigenetic regulation of tumor
• Author: Monika Mlinarić
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Polifenoli su sekundarni biljni metaboliti koji u ljudskom tijelu pokazuju pozitivne učinke
na različite bolesti, uključujući i tumore. Tumor nastaje kao posljedica genetskih i epigenetskih
promjena, a polifenoli mogu utjecati na inhibiciju razvoja i rasta tumora mijenjajući
reverzibilne epigenetske modifikacije. U ovom je radu opisan upravo učinak polifenola na
izmjenu aberantnih epigenetskih modifikacija u tumorskih stanica. Polifenoli su se pokazali kao
inhibitori DNA metiltransferaze pri čemu sprečavaju metilaciju DNA i omogućavaju
transkripcijsku aktivnost. Pokazali su učinak i na modifikacije histona (acetilaciju i metilaciju)
gdje aktivacijom ili inhibicijom uključenih enzima (histon acetil- i metil-tranferaze te histon
deacetilaze i demetilaze) mogu regulirati stanje kromatina, a preko toga i transkripciju. Treći
način regulacije genske ekspresije pokazan je u obliku smanjivanja ili povećavanja razine
ekspresije različitih miRNA koje onda utječu na ekspresiju ostalih faktora uključenih u
kancerogenezu. Preko ova tri mehanizma omogućena je regulacija transkripcijske aktivnosti što
je bitno za izmjenu nepravilnih ekspresija tumor-supresorskih gena i onkogena u tumorskih
stanica. Utišavanjem onkogena i reaktivacijom epigenetički utišanih tumor-supresor gena
polifenoli inhibiraju rast tumora. Iako daju dobre rezultate u uvjetima in vitro, polifenoli se još
uvijek ne mogu koristiti u svrhu terapije zbog nespecifičnog djelovanja na enzime, zbog tkivno
specifičnih epigenetskih modifikacija te zbog nedostupnosti u živom organizmu. Ukoliko se
riješe ovi problemi, polifenoli predstavljaju budućnost kemoprevencije i terapije tumora.

Abstract (english)

Polyphenols are secondary plant metabolites that show positive effects on various human
diseases, including tumors. Tumor appears as a result of genetic and epigenetic changes, and
polyphenols can affect the inhibition of tumor growth by altering the reversible epigenetic
modification. This paper describes the effect of polyphenols on the aberrant epigenetic
modification in tumor cells. Polyphenols have been shown to inhibit DNA methyltransferase
which results in inhibition of DNA methylation and activation of transcriptional activity. They
also demonstrated the effect on histone modification (acetylation and methylation) where
activation or inhibition of involved enzymes (histone acetyl- and methyl-tranferase, histone
deacetylase and demethylase) can regulate the chromatin state and with that a transcriptional
activity. The third model of regulation of gene expression has been shown to reduce or increase
the expression level of different miRNAs, which then influence the expression of other factors
involved in carcinogenesis. Through these three mechanisms it is possible to regulate
transcriptional activity which is essential for the modification of improper expression of tumorsuppressor
genes and oncogenes in tumor cells. By silencing of the oncogenes and the
reactivation of epigenetically silenced tumor-suppressor genes polyphenols inhibit tumor
growth. Although providing good results in in vitro conditions, polyphenols can not yet be used
for therapy because of non-specific action on enzymes, tissue-specific epigenetic modification
and lack of bioavailability in the living organism. If these problems are solved, polyphenols
represent the future of chemoprevention and tumor therapy.

• Keywords: polifenoli; tumori
• Keywords (english): polyphenols; tumors
• Language: croatian
• URN:NBN: urn:nbn:hr:217:008971
• Study programme: Title: Ecology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-09-28 10:44:03