Klin Farmakol Farm. 2015;29(3):108-112

The biologically active phospholipids isolated from egg yolk increasing cytotoxic effect of temozolomide

Jozef Hatok, Eva Blahovcová, Henrieta Škovierová, Radovan Murín
Univerzita Komenského v Bratislave, Jesseniova lekárska fakulta v Martine, Ústav lekárskej biochémie, Martin

on human glioblastoma cells

Extracts of biologically active phospholipids (BAP) may exert a positive effect on inhibition of tumor growth and may be used as additive

compounds to supplement palliative tumor treatment. The exact mechanisms by which BAP affect the cancer cells are still unknown.

Among brain tumors, glioblastoma multiforme (GBM) is considered the most aggressive and the most common primary brain tumor in

adults. The treatment of GBM includes surgery, radiotherapy and chemotherapy with an alkylating agent temozolomide (TMZ). With the

aim to study the survival of human glioblastoma cells, in media supplemented with BAP alone or in combination with TMZ, we used the

cell line T98G as a study model. The effect of BAP on glioblastoma cell survival was assessed by an methyl-thiazol tetrazolium (MTT) assay

and also microscopically. Cells were incubated in medium enriched with BAP of different final 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(

N-palmitoyl)ethanolamine (PNAE) concentrations in range 0,05 – 0,3 % (aBAP). Our results show that aBAP negatively affected the

cell survival, depending on their concentration in culture medium. Pre-culturing of the cells with aBAP for 24 hours before the incubation

with TMZ had potentiated the cytotoxic effect of TMZ on GBM cells. The results indicate that BAP with PNAE are capable to either inhibit

growth or induce the death of human glioblastoma cells in vitro. In conclusion, the capability of aBAP to potentiate the cytotoxic effect

of temozolomide indicates that further testing of aBAP as an adjunct agent to treat GBM, may be of great clinical significance.

Keywords: glioblastoma multiforme, chemoresistance, biologically active phospholipids, temozolomide

Published: December 1, 2015  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Hatok J, Blahovcová E, Škovierová H, Murín R. The biologically active phospholipids isolated from egg yolk increasing cytotoxic effect of temozolomide. Klin Farmakol Farm. 2015;29(3):108-112.
Download citation

References

  1. Küllenberg D, Taylor LA, Schneider M, Massing U. Health effects of dietary phospholipids. Lipids Health Dis 2012; 11: 3-18. Go to original source... Go to PubMed...
  2. Bednarčík P. Ovosan v podpůrné léčbě nádorových onemocnění - praktické zkušenosti. Sborník k semináři společnosti Areko(R) - Výzkum BAF(R) 2011-2012: 2-7.
  3. Brachwitz H, Vollgraf C. Analogs of alkyllysophospholipids: chemistry, effects on the molecular level and their consequences for normal and malignant cells. Pharmacol Ther 1995; 66: 39-82. Go to original source... Go to PubMed...
  4. Mikhaevich IS, Gerasimova GK, Kára J. Inhibition of protein kinase C by semisynthetic phospholipid plasmanyl-(N-acyl)-ethaolamine, a nontoxic antitumor preparation. Biochem Int 1991; 23: 215-220. Go to PubMed...
  5. Diba ChS, Pleško I, Hlava P. Incidencia zhubných nádorov v Slovenskej republike 2007. Bratislava: NHIC 2012.
  6. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 2002; 20: 1375-1382. Go to original source... Go to PubMed...
  7. Hart MG, Garside R, Rogers G, Stein K, Grant R. Temozolomide for high grade glioma. Cochrane Database Syst Rev 2013; 4: CD007415. Go to original source... Go to PubMed...
  8. Zhang J, Stevens MF, Bradshaw TD. Temozolomide: mechanisms of action, repair and resistance. Curr Mol Pharmacol 2012; 5: 102-114. Go to original source... Go to PubMed...
  9. Johannessen TCA, Bjerkvig R. Molecular mechanisms of temozolomide resistance in glioblastoma multiforme. Expert Rev Anticancer Ther 2012; 12: 635-642. Go to original source... Go to PubMed...
  10. Vojkovský T, Liebl V. N-acylované fosfolipidy typu 1-O-alkyl-sn-glycero-3-fosfoethanolaminů, způsob jejich semisyntetické přípravy a použití. CZ Patent 280 686, 1996.
  11. Kára J, Liebl V, Nováček A, Bejšovcová L. Způsob výroby přípravku s dieteticko-preventivním a léčebným účinkem na bázi vaječných 1-O-alkyl-2-acyl-fosfatidylethanolaminů. CZ Patent 282 139, 1997.
  12. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 1983; 65: 55-63. Go to original source... Go to PubMed...
  13. Hatok J, Matáková T, Jurečeková J, et al. Naše päťročné výsledky in vitro testovania chemorezistencie u onkologických pacientov. Klin Onkol 2011; 24: 443-446. Go to PubMed...
  14. Shuman Moss LA, Jensen-Taubman S, Rubinstein D, Viole G, Stetler-Stevenson WG. Dietary intake of a plant phospholipid/lipid conjugate reduces lung cancer growth and tumor angiogenesis. Carcinogenesis 2014; 35: 1556-1563. Go to original source... Go to PubMed...
  15. Sakakima Y, Hayakawa A, Nagasaka T, Nakao A. Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in vivo experiments. J Hepatol 2007; 47: 83-92. Go to original source... Go to PubMed...
  16. Marco C, Ríos-Marco P, Jiménez-López JM, Seqovia JL, Carrasco MP. Antitumoral alkylphospholipids alter cell lipid metabolism. Anticancer Agents Med Chem 2014; 14: 545-558. Go to original source... Go to PubMed...
  17. Semini G, Hildmann A, von Haefen C, Danker K. Glycosidated phospholipids - a promising group of anti-tumour lipids. Anticancer Agents Med Chem 2014; 14: 607-617. Go to original source... Go to PubMed...
  18. Arthur G, Bittman R. Glycosylated antitumor ether lipids: activity and mechanism of action. Anticancer Agents Med Chem 2014; 14: 592-606. Go to original source... Go to PubMed...
  19. Engebraaten O, Bjerkvig R, Berens ME. Effect of alkyl-lysophospholipid on glioblastoma cell invasion into fetal rat brain tissue in vitro. Cancer Res 1991; 51: 1713-1719.
  20. Li YC, Park MJ, Ye SK, Kim CW, Kim YN. Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol 2006; 168: 1107-1118. Go to original source... Go to PubMed...
  21. Kára J, Konovalova AL, Krasnova MA, Liebl V, Bejsovcová L. New tumoricidal semisynthetic ether phospholipid, plasmanyl-(N-acyl)ethanolamine (PNAE(s)) and enhancement of its tumoricidal activity by calcium ions. Neoplasma 1993; 40: 213-217. Go to PubMed...
  22. Verheij M, Moolenaar WH, van Blitterswijk WJ. Combining anti-tumor alkyl-phospholipid analogs and radiotherapy: rationale and clinical outlook. Anticancer Agents Med Chem 2014; 14: 618-628. Go to original source... Go to PubMed...
  23. Mrugala MM. Advances and challenges in the treatment of glioblastoma: a clinician's perspective. Discov Med 2013; 15: 221-230. Go to PubMed...




Clinical Pharmacology and Pharmacy

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.