Ukr.Biochem.J. 2021; Volume 93, Issue 3, May-Jun, pp. 49-60

doi: https://doi.org/10.15407/ubj93.03.049

Comparative cytotoxic activity of carboplatin and β-cryptoxanthin in free and liposomal forms against breast cancer cell line

M. W. Shafaa*, N. S. Elkholy

Physics Department, Medical Biophysics Division, Faculty of Science,
Helwan University, Cairo, Egypt;
*e-mail: medhatwi@hotmail.com

Received: 1 June 2020; Accepted: 17 May 2021

The study of the effectiveness of the synthetic and natural anticarcinogenic compounds in liposomal form is urgent for their possible use in therapy. In this work, the alkylating agent carboplatin and the representative of carotenoids β-cryptoxanthin were used. The aim of the research was to study the toxicity of these compounds in free and liposomal forms against breast cancer MCF-7 cell line. According to DSC and FTIR data, when carboplatin or β-cryptoxanthin were added to liposomal bilayers, a single peak was observed indicating their mutual mixing. Integration of  β-cryptoxanthin into bilayer was found to be more proper for the creation of PE acyl chains ordered and cooperative state. It was found that MCF-7 cells sensitivity was much higher to the free β-cryptoxanthin than to the free carboplatin with IC50 42 and 235 μg/ml, respectively. The IC50 values for β-cryptoxanthin loaded into liposomes and for free carboplatin were similar. At the same time, no cytotoxic effect of carboplatin-loaded liposomes was observed. The data obtained allow proposing a possible antitumor treatment regimen where carboplatin is replaced by free β-cryptoxanthin or its liposomal form to increase the effectiveness of breast cancer therapy.

Keywords: , , , , , ,


References:

  1. Tarver T. Cancer facts & figures, American cancer society (ACS) Atlanta, GA: American Cancer Society; 2012. P. 66.
  2. Talluri SV, Kuppusamy G, Karri VV, Tummala S, Madhunapantula SV. Lipid-based nanocarriers for breast cancer treatment – comprehensive review. Drug Deliv. 2016;23(4):1291-1305. PubMed, CrossRef
  3. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975-999. PubMed, PubMedCentral, CrossRef
  4. Bangham AD, Hill MW, Miller NGA. In: Methods in Membrane Biology (Korn N.D., ed.) Plenum. N.Y., 1974. Vol.1, p.l.
  5. Riaz M. Liposomes preparation methods. Pak J Pharm Sci. 1996;9(1):65-77.   PubMed
  6. Chang RS, Kim J, Lee HY, Han SE, Na J, Kim K, Kwon IC, Kim YB, Oh YK. Reduced dose-limiting toxicity of intraperitoneal mitoxantrone chemotherapy using cardiolipin-based anionic liposomes. Nanomedicine. 2010;6(6):769-776. PubMed, CrossRef
  7. Hwang JS, Tsai YL, Hsu KC. The feasibility of antihypertensive oligopeptides encapsulated in liposomes prepared with phytosterols-β-sitosterol or stigmasterol. Food Res Int. 2010;43(1):133–139. CrossRef
  8. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev. 2010;4(8):118-126. PubMed, PubMedCentral, CrossRef
  9. Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol. 1999;17(1):409-422. PubMed, CrossRef
  10. Perez EA. Carboplatin in combination therapy for metastatic breast cancer. Oncologist. 2004;9(5):518-527. PubMed, CrossRef
  11. Milner JA. Molecular targets for bioactive food components. J Nutr. 2004;134(9):2492S-2498S. PubMed, CrossRef
  12. Kris-Etherton PM, Hecker KD, Bonanome A, Coval SM, Binkoski AE, Hilpert KF, Griel AE, Etherton TD. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med. 2002;113(Suppl 9B):71S-88S.  PubMed, CrossRef
  13. Seshadri TR. Biochemistry of natural pigments; (exclusive of haeme pigments and carotenoids). Annu Rev Biochem. 1951;20:487-512.  PubMed, CrossRef
  14. Bartley GE, Scolnik PA. Plant carotenoids: pigments for photoprotection, visual attraction, and human health. Plant Cell. 1995;7(7):1027-1038. PubMed, PubMedCentral, CrossRef
  15. Handelman GJ. The evolving role of carotenoids in human biochemistry. Nutrition. 2001;17(10):818-822. PubMed, CrossRef
  16. Johnson EJ. The role of carotenoids in human health. Nutr Clin Care. 2002;5(2):56-65. PubMed, CrossRef
  17. Stahl W, Sies H. Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta. 2005;1740(2):101-107. PubMed, CrossRef
  18. Katsuura S, Imamura T, Bando N, Yamanishi R. beta-Carotene and beta-cryptoxanthin but not lutein evoke redox and immune changes in RAW264 murine macrophages. Mol Nutr Food Res. 2009;53(11):1396-1405. PubMed, CrossRef
  19. Unno K, Sugiura M, Ogawa K, Takabayashi F, Toda M, Sakuma M, Maeda K, Fujitani K, Miyazaki H, Yamamoto H, Hoshino M. Beta-cryptoxanthin, plentiful in Japanese mandarin orange, prevents age-related cognitive dysfunction and oxidative damage in senescence-accelerated mouse brain. Biol Pharm Bull. 2011;34(3):311-317. PubMed, CrossRef
  20. Eid SY, El-Readi MZ, Wink M. Carotenoids reverse multidrug resistance in cancer cells by interfering with ABC-transporters. Phytomedicine. 2012;19(11):977-987. PubMed, CrossRef
  21. Deamer DW, Uster PS: In liposomes. (Ostro M.J.,Ed), Dekker, New York; 1983. p.27-51.
  22. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990;82(13):1107-1112. PubMed, CrossRef
  23. Paolino D, Fresta M, Sinha P, Ferrari M. Drug delivery systems. In: Webster JG (ed.) Encyclopedia of medical devices and instrumentation, 2nd edn. Wiley, New York, 2006. P. 437–495. CrossRef
  24. Klein JW, Ware BR, Barcla G, Petty HR. Phospholipid dependence of calcium ion effects on electrophoretic mobilities of liposomes. Chem Phys Lipids. 1987;43(1):13-23. PubMed, CrossRef
  25. Law SL, Lo WY, Pai SH, Teh GW. The electrokinetic behavior of liposomes adsorbed with bovine serum albumin. Int J Pharmac. 1988;43(3):257-260. CrossRef
  26. Makino K, Yamada T, Kimura M, Oka T, Ohshima H, Kondo T. Temperature- and ionic strength-induced conformational changes in the lipid head group region of liposomes as suggested by zeta potential data. Biophys Chem. 1991;41(2):175-183. PubMed, CrossRef
  27. Plank L, Dahl CE, Ware BR. Effect of sterol incorporation on head group separation in liposomes. Chem Phys Lipids. 1985;36(4):319-328. PubMed, CrossRef
  28. Koynova R, Caffrey  M. Phases and phase transitions of the phosphatidylcholines. Biochim Biophys Acta. 1998;1376(1):91-145. PubMed, CrossRef
  29. Mady MM, Shafaa MW, Abbase ER, Fahium AH. Interaction of doxorubicin and dipalmitoylphosphatidylcholine liposomes. Cell Biochem Biophys. 2012;62(3):481-486. PubMed, CrossRef
  30. Severcan F, Sahin I, Kazanci N. Melatonin strongly interacts with zwitterionic model membranes—evidence from Fourier transform infrared spectroscopy and differential scanning calorimetry. Biochim Biophys Acta. 2005;1668(2):215-222. PubMed, CrossRef
  31. Mady MM, Fathy MM, Youssef T, Khalil WM. Biophysical characterization of gold nanoparticles-loaded liposomes. Phys Med. 2012;28(4):288-295. PubMed, CrossRef

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