Author: Helga Engi 1
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  • 1 Faculty of Medicine, University of Szeged Department of Medical Microbiology and Immunobiology Dóm tér 10 H-6720 Szeged Hungary
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The development of pharmacological agents able to counteract the mechanisms of multidrug resistance (MDR) in oncology has remained a major goal for the past ten years. Several mechanisms are thought to be involved in drug resistance, including those associated with drug transport, detoxification and apoptosis. The first part of this thesis was focused on the inhibition of MDR through inhibition of the MDR P-glycoprotein (P-gp) in various cell lines. Six groups of compounds were involved in the P-gp efflux pump inhibitory studies: cinnamylidene ketones; 1,4-dihydropyridines derivatives; phenothiazines; HSP90 inhibitor peptide derivatives; Tylosin Betti base derivative and Euphorbia diterpenes. The majority of the tested compounds were able to increase the R123 accumulation in cancer cell lines. Generally, the newly identified MDR modifiers were able to enhance the antiproliferative activity of selected anticancer drugs in a synergistic or additive way in vitro on MDR cells. The in vitro activity of TBN was confirmed in further in vivo efficacy studies in DBA/2 mice. As an alternative way of antitumour effect, apoptosis inductions of resistance modifiers were studied. The substituted dihydropyridine 13 was the most promising apoptosis inducer on L 5178 Y cells. The human cytomegalovirus (CMV) was used in a modified in vitro model for characterizing lathyrane compounds with antipromotion effect on human lung cancer cells. All the six macrocyclic lathyrane-type diterpenoids, except latilagascene D, could reduce the promotion in vitro decreased IE-antigen expression of CMV to prevent progression of tumour malignancy.

  • Pajak, B., Molnár, J., Engi, H. et al.: Preliminary studies on Phenothiazine-mediated reversal of multidrug resistance in mouse lymphoma and COLO 320 cells. In Vivo, 2005, 19 , 1101–1104.

    Engi H. , 'Preliminary studies on Phenothiazine-mediated reversal of multidrug resistance in mouse lymphoma and COLO 320 cells ' (2005 ) 19 In Vivo : 1101 -1104.

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  • Engi, H., Gyémánt, N., Lóránd, T. et al.: Cinnamylidene ketones as potential modulators of multidrug resistance in mouse lymphoma and human colon cancer cell lines. In Vivo, 2006, 20 , 119–124.

    Lóránd T. , 'Cinnamylidene ketones as potential modulators of multidrug resistance in mouse lymphoma and human colon cancer cell lines ' (2006 ) 20 In Vivo : 119 -124.

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  • Engi, H., Sakagami, H., Kawase, M. et al.: Tumour-specific cytotoxicity and MDR-reversal activity of dihydropyridines. In Vivo, 2006, 20 , 637–644.

    Kawase M. , 'Tumour-specific cytotoxicity and MDR-reversal activity of dihydropyridines ' (2006 ) 20 In Vivo : 637 -644.

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  • Molnár, J., Engi, H., Mándi, Y. et al.: Effects of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells. In Vivo, 2007, 21 , 429–434.

    Mándi Y. , 'Effects of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells ' (2007 ) 21 In Vivo : 429 -434.

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  • Pusztai, R., Ferreira, M. J. U., Duarte, N., Engi, H. et al.: Macrocyclic lathyrane diterpenes as antitumor promoters. Anticancer Res., 2007, 27 , 201–206.

    Engi H. , 'Macrocyclic lathyrane diterpenes as antitumor promoters ' (2007 ) 27 Anticancer Res. : 201 -206.

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  • Engi, H., Vasas, A., Rédei, D, et al.: New MDR modulators and apoptosis inducer from Euphorbia species. Anticancer Res., 2007, 27 , 3451–3458.

    Rédei D. , 'New MDR modulators and apoptosis inducer from Euphorbia species ' (2007 ) 27 Anticancer Res. : 3451 -3458.

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  • Amaral, L., Viveiros, M., Engi, H. et al.: Comparison of multidrug resistant efflux pumps of bacteria and cancer cells with respect to the same inhibitory agents. In Vivo, 2007, 21 , 237–244.

    Engi H. , 'Comparison of multidrug resistant efflux pumps of bacteria and cancer cells with respect to the same inhibitory agents ' (2007 ) 21 In Vivo : 237 -244.

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  • Engi, H., Gyémánt, N., Lóránd, T. et al.: Cinnamilidén-cikloalkánonok és cinnamilidén-benzocikloalkanonok multidrog rezisztencia módosító hatása tumorsejteken. (Multidrug resistance reversal effects of cinnamylidene-cycloalkanes and cinnamylidene-benzocycloalkanes on tumour cells.) (In Hungarian). Erdélyi Múzeum-Egyesület, Orvostudományi Értesítő, 2005, 78 , 574–578.

    Lóránd T. , 'Cinnamilidén-cikloalkánonok és cinnamilidén-benzocikloalkanonok multidrog rezisztencia módosító hatása tumorsejteken ' (2005 ) 78 Erdélyi Múzeum-Egyesület, Orvostudományi Értesítő : 574 -578.

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