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Bersavine: A Novel Bisbenzylisoquinoline Alkaloidwith Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells
D. Koutova, M. Kulhava, R. Havelek, M. Majorosova, K. Královec, K. Habartova, A. Hošťálková, L. Opletal, L. Cahlikova, M. Řezáčová,
Language English Country Switzerland
Document type Journal Article
Grant support
CZ.02.1.01/0.0/0.0/18_069/0010046
European Union
Progres/UK Q40/01
Charles University
SVV-260397/2017
Charles University
NLK
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- MeSH
- Alkaloids * chemistry isolation & purification pharmacology MeSH
- Apoptosis drug effects MeSH
- Berberis chemistry MeSH
- Hep G2 Cells MeSH
- HT29 Cells MeSH
- Cytotoxins * chemistry isolation & purification pharmacology MeSH
- Antineoplastic Agents, Phytogenic * chemistry isolation & purification pharmacology MeSH
- G1 Phase drug effects MeSH
- HeLa Cells MeSH
- Jurkat Cells MeSH
- Leukemia drug therapy metabolism pathology MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Drug Screening Assays, Antitumor MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L.(Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed thatbersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon(HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 μM.The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavinetreatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependentantiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell linesusing a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavineat 20 μM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method.The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. Theupregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cellapoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity ofcaspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylationand decreased Rb Ser807/811 phosphorylation in human leukemic cells.
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- $a Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L.(Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed thatbersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon(HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 μM.The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavinetreatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependentantiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell linesusing a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavineat 20 μM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method.The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. Theupregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cellapoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity ofcaspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylationand decreased Rb Ser807/811 phosphorylation in human leukemic cells.
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