7 research outputs found

    Chelidonin a Homochelidonin indukují buněčnou smrt prostřednictvím drah checkpoint a MAP kináz

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    This study focuses on the comparative in vitro cytotoxicity of chelidonine and homochelidonine on human cancer and non-cancer cells. Both alkaloids produced a decrease in cellular growth in a dose-dependent manner exhibiting greater potency in cancer cells. The growth inhibitory effect was evidenced in both ovarian carcinoma A2780 and lung fibroblast MRC-5 cells by inducing G2 and mitotic phase cell cycle arrest. Results indicated that the extent of apoptosis induced by chelidonine and homochelidonine was correlated to sensitivity to the antiproliferative activity of the evaluated compounds. Western blotting suggested that the cellular toxicological mechanism of chelidonine is related to the differential upregulation of phospho-Chk2, p21(Cip1/Waf1), phospho-ERK1/2 and phospho-p38 in various cell types, leading to alternations in the suppression of proliferation and either induction or prevention of apoptosis. Chelidonine showed the more potent effects and also affected the cell cycle checkpoints and MAPK signaling pathways within cells.Tato práce je zaměřena na srovnávací cytotoxicitu chelidoninu a homochelidoninu na lidských nádorových a nenádorových buňkách

    Protinádorový potenciál alkaloidů čeledi Amaryllidaceae testovaný na panelu lidských linií, pomocí analýzy buněk v reálném čase a na Ehrlichově nádoru myší

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    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 mu M 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 mM 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.V této studii byl testován protinádorový potenciál 22 alkaloidů čeledi Amaryllidaceae na panelu lidských linií, pomocí analýzy buněk v reálném čase a na Ehrlichově nádoru myší

    Porovnání cytotoxicity chelidoninu a homochelidoninu, dimethoxy analoga izolovaného z Chelidonium majus L. (Papaveraceae), vůči lidským leukemickým a plicním nádorovým buňkám

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    In this study the effects of naturally occurring homochelidonine in comparison to chelidonine on cell cycle progression and cell death in leukemic T-cells with different p53 status are described. We found that homochelidonine and chelidonine displayed significant cytotoxicity in examined blood cancer cells with the exception of HEL 92.1.7 and U-937 exposed to homochelidonine. Unexpectedly, homochelidonine and chelidonine-induced cytotoxicity was more pronounced in Jurkat cells contrary to MOLT-4 cells. Homochelidonine showed an antiproliferative effect on A549 cells but it was less effective compared to chelidonine. Biphasic dose-depended G1 and G2/M cell cycle arrest along with the population of sub-G1 was found after treatment with homochelidonine in MOLT-4 cells. In variance thereto, an increase in G2/M cells was detected after treatment with homochelidonine in Jurkat cells. Treatment with chelidonine induced cell cycle arrest in the G2/M cell cycle in both MOLT-4 and Jurkat cells. MOLT-4 and Jurkat cells treated with homochelidonine and chelidonine showed features of apoptosis such as phosphatidylserine exposure, a loss of mitochondrial membrane potential and an increase in the caspases -3/7, -8 and -9. Western blots indicate that homochelidonine and chelidonine exposure activates Chk1 and Chk2. Studies conducted with fluorescence microscopy demonstrated that chelidonine and homochelidonine inhibit tubulin polymerization in A549 cells. Collectively, the data indicate that chelidonine and homochelidonine are potent inducers of cell death in cancer cell lines, highlighting their potential relevance in leukemic cells.Tato práce porovnává cytotoxicitu chelidoninu a homochelidoninu vůči lidským leukemickým a plicním nádorovým buňkám. Výsledky studie naznačují, že chelidonin a homochelidonin jsou účinnými aktivátory apoptózy u nádorových buněčných linií

    Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells

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    Abstract Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug
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