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Anticancer potential of Amaryllidaceae alkaloids evaluated by screening with a panel of human cells, real-time cellular analysis and Ehrlich tumor-bearing mice

R. Havelek, D. Muthna, P. Tomsik, K. Kralovec, M. Seifrtova, L. Cahlikova, A. Hostalkova, M. Safratova, M. Perwein, E. Cermakova, M. Rezacova,

. 2017 ; 275 (-) : 121-132. [pub] 20170726

Language English Country Ireland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17030664

In this study, twenty-two Amaryllidaceae alkaloids were screened for their anticancer potential. All isolates were evaluated for antiproliferative activities on a panel of 17 human cell types of different tissue origin using WST-1 assay. In addition, we determined the antiproliferative effect with a real-time cell analysis xCELLigence system. Thereafter, to evaluate the barely known in vivo anticancer potential of the most potent molecule haemanthamine, a preliminary study was performed using an Ehrlich tumor-bearing mice model. The results showed that haemanthamine, lycorine and haemanthidine exerted the highest antiproliferative activity. The mean growth percent (GP) value after a single-dose 10 μM treatment was for haemanthamine 21%, for lycorine 21% and for haemanthidine 27% that of untreated control cells (100%). Furthermore, haemanthamine, lycorine and haemanthidine exhibited significant cytotoxicities against all the tested cell lines with individual IC50 values in the micromolar range. Dynamic real-time measures of impedance by xCELLigence indicated that these three compounds suppress cell proliferation after 10 h of treatment at a concentration of 10 μM or higher. Regrettably, in a follow-up in vivo antitumor activity study, haemanthamine showed no statistically significant reduction in the tumor size with no prolongation of survival time of Ehrlich tumor-bearing mice. Taken together, these results provide a new clue and guidance for exploiting Amaryllidaceae alkaloids as anticancer agents.

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$a In this study, twenty-two Amaryllidaceae alkaloids were screened for their anticancer potential. All isolates were evaluated for antiproliferative activities on a panel of 17 human cell types of different tissue origin using WST-1 assay. In addition, we determined the antiproliferative effect with a real-time cell analysis xCELLigence system. Thereafter, to evaluate the barely known in vivo anticancer potential of the most potent molecule haemanthamine, a preliminary study was performed using an Ehrlich tumor-bearing mice model. The results showed that haemanthamine, lycorine and haemanthidine exerted the highest antiproliferative activity. The mean growth percent (GP) value after a single-dose 10 μM treatment was for haemanthamine 21%, for lycorine 21% and for haemanthidine 27% that of untreated control cells (100%). Furthermore, haemanthamine, lycorine and haemanthidine exhibited significant cytotoxicities against all the tested cell lines with individual IC50 values in the micromolar range. Dynamic real-time measures of impedance by xCELLigence indicated that these three compounds suppress cell proliferation after 10 h of treatment at a concentration of 10 μM or higher. Regrettably, in a follow-up in vivo antitumor activity study, haemanthamine showed no statistically significant reduction in the tumor size with no prolongation of survival time of Ehrlich tumor-bearing mice. Taken together, these results provide a new clue and guidance for exploiting Amaryllidaceae alkaloids as anticancer agents.
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$a Muthna, Darina $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, Hradec Kralove 500 03, Czech Republic.
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$a Tomsik, Pavel $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, Hradec Kralove 500 03, Czech Republic.
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$a Kralovec, Karel $u Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic.
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$a Seifrtova, Martina $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, Hradec Kralove 500 03, Czech Republic.
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$a Cahlikova, Lucie $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, Hradec Kralove 500 05, Czech Republic. Electronic address: cahlikova@faf.cuni.cz.
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$a Hostalkova, Anna $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, Hradec Kralove 500 05, Czech Republic.
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$a Safratova, Marcela $u ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, Hradec Kralove 500 05, Czech Republic.
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$a Perwein, Maria $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, Hradec Kralove 500 03, Czech Republic.
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$a Cermakova, Eva $u Department of Medical Biophysics, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, Hradec Kralove 500 03, Czech Republic.
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$a Rezacova, Martina $u Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, Hradec Kralove 500 03, Czech Republic.
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