Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2010, vol. 19, nr 4, July-August, p. 481–487

Publication type: original article

Language: English

Effect of Polyunsaturated Fatty Acids on Doxorubicin Cytotoxicity in Glioma Cells in vitro

Wpływ wielonienasyconych kwasów tłuszczowych na cytotoksyczność doksorubicyny w komórkach glejaków in vitro

Alicja Zajdel1,, Adam Wilczok1,, Małgorzata Latocha2,, Zofia Dzierżewicz1,

1 Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland

2 Department of Cell Biology, Medical University of Silesia, Sosnowiec, Poland

Abstract

Background. In normal and tumour cells, polyunsaturated fatty acids (PUFAs) act as intracellular second messengers, which play a role in signalling, proliferation and cell death. PUFAs have selective tumouricidal action and may alter sensitivity of tumour cells to radiation and chemotherapy.
Objectives. Investigation of the ability of exogenous linoleic acid (LA, 18:2 n-6), α-linolenic acid (ALA, 18:3 n-3), arachidonic acid (AA, 20:4 n-6), eicosapentaenoic acid (EPA, 20:5 n-3), and docosahexaenoic acid (DHA, 22:6 n-3) to modulate sensitivity of human glioma cells to doxorubicin.
Material and Methods. The influence of PUFAs (0–100 μM) on the viability of human foreskin fibroblasts (HFF-1), human glioblastoma (SNB-19), and human gliomas (8-MG-BA, 42-MG-BA) grown in the absence or presence of doxorubicin was estimated. Viability of the cells was measured after 72 hours of exposure by the WST-1 tetrazolium salt assay.
Results. DHA (25 μM) stimulated growth of fibroblasts, while LA (50 and 100 μM) and AA (100 μM) reduced their growth. Glioma cell growth was not stimulated by the tested fatty acids. EPA (100 μM) and DHA (100 μM) inhibited viability of 8-MG-BA and 42-MG-BA glioma cells. SNB-19 glioblastoma cells remained resistant to PUFAs. PUFAs did not modify growth of the fibroblasts exposed to doxorubicin. PUFAs (100 μM), in particular DHA, enhanced doxorubicin cytotoxicity in all glioma cell lines used. At lower concentrations, EPA (25 μM) and DHA (25 μM) decreased doxorubicin toxicity in SNB-19 cells. Similar effect was observed for ALA (25 μM) and AA (25 μM) in 8-MG-BA cells. Conclusion. To increase doxorubicin antitumour activity in glioma cell lines high concentrations of PUFAs are required. At low concentrations of PUFAs this activity can be diminished. These facts should be taken into consideration in therapy for patients with brain gliomas.

Streszczenie

Wprowadzenie. Zarówno w komórkach prawidłowych, jak i nowotworowych wielonienasycone kwasy tłuszczowe (w.n.k.t.) pełnią funkcję wewnątrzkomórkowych, drugorzędowych przekaźników sygnału w procesach proliferacji oraz śmierci komórki. W.n.k.t. wykazują selektywne działanie przeciwnowotworowe i mogą wpływać na wrażliwość komórek nowotworowych na naświetlanie i chemioterapię.
Cel pracy. Zbadanie zdolności egzogennych kwasów tłuszczowych: linolowego (LA, 18:2 n-6), α-linolenowego (ALA, 18:3 n-3), arachidonowego (AA, 20:4 n-6), eikozapentaenowego (EPA, 20:5 n-3) i dokozaheksaenowego (DHA, 20:6 n-3) do modulowania wrażliwości ludzkich komórek glejaków na doksorubicynę. Materiał i Metody. Do oznaczenia wpływu w.n.k.t. (0–100 μM) na przeżywalność ludzkich komórek fibroblastów napletka (HFF-1), glejaka wielopostaciowego (SNB-19), ludzkich glejaków (8-MG-BA, 42-MG-BA) hodowanych w nieobecności i obecności doksorubicyny zastosowano test WST-1. Przeżywalność komórek była mierzona po 72 godzinach ekspozycji.
Wyniki. DHA (25 μM) stymulował wzrost fibroblastów w przeciwieństwie do LA (50 i 100 μM) oraz AA (100 μM), które hamowały ich wzrost. Badane kwasy tłuszczowe nie stymulowały wzrostu komórek glejaków. EPA (100 μM) oraz DHA (100 μM) zmniejszały przeżywalność komórek glejaków linii 8-MG-BA i 42-MG-BA. Komórki glejaka wielopostaciowego SNB-19 nie wykazały wrażliwości na w.n.k.t. W.n.k.t. nie modyfikowały wzrostu fibroblastów eksponowanych na doksorubicynę. W.n.k.t. (100 μM), w szczególności DHA, zwiększały cytotoksyczność doksorubicyny wobec wszystkich testowanych linii glejaków. W mniejszych stężeniach EPA (25 μM) oraz DHA (25 μM) zmniejszały cytotoksyczność doksorubicyny w linii komórek SNB-19. Podobne działanie zaobserwowano w przypadku ALA (25 μM) i AA (25 μM) w komórkach 8-MG-BA.
Wnioski. Zwiększenie aktywności przeciwnowotworowej doksorubicyny wobec komórek linii glejaków wymaga zastosowania w.n.k.t. w dużych stężeniach. W małych stężeniach kwasy te mogą spowodować zmniejszenie przeciwnowotworowej aktywności doksorubicyny. Fakty te powinny być brane pod uwagę w leczeniu pacjentów z glejakami mózgu.

Key words

polyunsaturated fatty acids, doxorubicin, glioma cells

Słowa kluczowe

wielonienasycone kwasy tłuszczowe, doksorubicyna, komórki glejaków

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