Molecular mechanisms of action of phytochemicals as anticancer agents

Rak je poligenska bolezen, ki nastane zaradi mutacij ali epigenetskih sprememb v dednem zapisu normalne celice ter zaradi staranja prebivalstva in številnih okoljskih vzrokov predstavlja zdravstveni izziv svetovnih razsežnosti. Zdravljenje rakavih bolnikov je lahko kirurško, z obsevanjem ali sistemsko zdravljenje s citostatiki (t. j. s kemoterapijo), hormonskimi zdravili in tarčnimi zdravili. Zaradi potencialne toksičnosti in pomanjkanja selektivnosti teh zdravil se pojavlja vedno več raziskav alternativnih načinov zdravljenja. Pri tem izstopajo kemikalije rastlinskega izvora oziroma fitokemikalije, ki imajo velik potencial pri zdravljenju raka zaradi številnih mehanizmov delovanja, raznolikosti kemijskih struktur, razpoložljivosti v naravi in relativno nizke toksičnosti. V organizmu imajo različne tarčevplivajo lahko na apoptotične poti, genetske in epigenetske mutacije, poškodbe deoksiribonukleinskih kislin, proizvodnjo reaktivnih kisikovih spojin, avtofagijo, invazijo in metastaziranje rakavih celic, modulacijo celičnih signalov itd. Številne fitokemikalije farmakološko preučujejo zaradi njihovega kemopreventivnega in kemoterapevtskega potenciala. V poskusih in vitro in študijah na živalih so pokazali tudi antiproliferativne, proapoptotične, antimetastatične in antiangiogene učinke večjega števila fitokemikalij. Namen diplomskega dela je pregled znanstvenih člankov na temo fitokemikalij, uporabljenih za zdravljenje ali podporno zdravljenje rakavih obolenj in opredelitev možnih molekularnih mehanizmov protirakavega delovanja različnih fitokemikalij na rakave celice.Cancer is a polygenic disease caused by mutations or epigenetic changes in the hereditary blueprint of a normal cell and, due to the aging population and numerous environmental factors, represents a health challenge of global proportions. Cancer patients can be treated with surgery, radiation or systemic treatment with cytostatics (i.e., chemotherapy), hormonal drugs and targeted drugs. The potential toxicity and lack of selectivity of these drugs has led to increasing research into alternative treatments. Plant-derived chemicals, or phytochemicals, stand out as having great potential in cancer treatment due to their multiple mechanisms of action, variety of chemical structures, availability in nature and relatively low toxicity. They have different targets in the organismthey can affect apoptotic pathways, genetic and epigenetic mutations, deoxyribonucleic acid damage, production of reactive oxygen species, autophagy, cancer cell invasion and metastasis, modulation of cell signalling, etc. Many phytochemicals are being studied pharmacologically for their chemopreventive and chemotherapeutic potential. However, in vitro experiments and animal studies have also shown antiproliferative, proapoptotic, antimetastatic and antiangiogenic effects of numerous phytochemicals. The aim of this thesis is to review the scientific literature on phytochemicals used for the treatment or supportive care of cancer and to identify possible molecular mechanisms of anticancer action of different phytochemicals on cancer cells