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Citotoksično dejstvo ekstrakata biljke Sideritis Scardica na tumorske ćelije u in vitro uslovima

Cytotoxic effects of Sideritis scardica extracts against tumor cells in vitro

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2013
Disertacija.pdf (2.533Mb)
Author
Jeremić, Ivica P.
Mentor
Isaković, Aleksandra
Committee members
Tadić, Vanja
Trajković, Vladimir
Marković, Ivanka
Rakić, Ljubisav
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Abstract
Sideritis scardica Griseb, Lamiaceae (Šarplaninski čaj) je endemska biljka Balkanskog poluostrva, koja se tradicionalno koristi za lečenje astme, bronhitisa, gastričnih i reumatskih tegoba. Cilj ovog istraživanja je bio da se ispita citotoksični efekat različito frakcionisanih ekstrakata na tumorskse ćelijske linije: humane promijelocitne leukemije HL-60, mišjeg melanoma B16 i pacovskog glioma C6 u in vitro uslovima. Rezultati su pokazali značajan citotoksični efekat ekstrakta S. scardica na sve testirane tumorske linije Pokazano je da se među identifikovanim, aktivnim jedinjenjima, flavonoidima apigeninu i luteolinu može pripisati odgovornost za citotoksičnost ekstrakata. Posebno je značajno da ovi ekstrakti nisu bili toksični za primarne pacovske astrocite i mononuklearne ćelije periferne krvi čoveka. Mehanizam citotoksičnosti koju su dietil-etarski i etil-acetatni ekstrakt S.scardica ispoljili prema tumorskim ćelijskim linijama je kompleksan i uključuje indukciju apoptoze, autofagij...e i zastoja u ćelijskom ciklusu. Dietil-etarski i etil-acetatni ekstrakt, kao i citotoksične fenolne komponente apigenin i luteolin indukuju AMPK/Akt/mTOR nezavisnu autofagiju u tretiranim C6 ćelijama glioma. Kombinovana primena karmustina i ekstrakata, dovodi do smanjenja citotoksičnosti karmustina prema C6 ćelijama. Sa druge strane, C6 ćelije tretirane netoksičnim dozama dietil-etarskog i etil-acetatnog ekstrakta, postaju znatno osetljivije na delovanje UV zračenja. Za razliku od njih, primarni astrociti, tretirani istim dozama ekstrakata postaju rezistentniji na UV zračenje. Imajući u vidu bogatsvo flavonoidima i mnogostruke mehanizme antitumorskog delovanja S. scardica bi mogla da se ubroji u tzv. funkcionalnu hranu sa hemopreventivnim svojstvima.

Sideritis scardica (Mountain tea) is endemic plant of Balcan Peninsula traditionally used to cure asthma, bronchitis, rheumatic disorders and gastric complaints. The aim of this study was to investigate cytotoxic effect of different S. scardica extracts on tumor cell lines: human promyelocitic leukemia HL-60, mouse melanoma B16 and rat glioma C6. The results showed significant cytotoxic effect of diethyl ether and ethyl acetate extracts on all tested tumor lines. As main active principles, flavonoids apigenin and luteolin were identified. Additionally, extracts were not toxic for either rat astrocytes in primary cultures, and human peripherial blood mononuclear cells. The mechanism of citotoxicity is rather complex and includes apoptosis and autophagy induction, as well cell cycle arrest. Diethyl ether and ethyl acetate extracts, as well cytotoxic compound apigenin and luteolin induced AMPK/Akt/mTOR independent autophagy in treated glioma cells. The combinatorial use of carmustine and ...extracts, lead to a decreassed toxicity of carmustine against C6 cells. C6 cells treated with non-toxic dooses of extracts were more susceptible to UV light induced cytotoxicity. Contrary, rat astrocytes in primary cultures, treated with the same concentrations of extracts, were more resistant to UV irradiation. Considering rich flavonoid content, as well as multiple mechanisms underlying their antitumor actions, S scardica could be regarded as functional food with chemopreventive properties

Faculty:
University of Belgrade, School of Medicine
Date:
29-05-2013
Projects:
  • Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-41025)
Keywords:
ekstrakti / extracts / S. scardica / apoptoza / autofagija / S. scardica / apoptosis / autophagy
[ Google Scholar ]
URI
http://nardus.mpn.gov.rs/handle/123456789/2376
http://eteze.bg.ac.rs/application/showtheses?thesesId=668
https://fedorabg.bg.ac.rs/fedora/get/o:6894/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=44668943

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