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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,
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
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
Directory of Open Access Journals
od 1997
Free Medical Journals
od 1997
PubMed Central
od 2001
Europe PubMed Central
od 2001
ProQuest Central
od 1997-01-01
Open Access Digital Library
od 1997-01-01
Medline Complete (EBSCOhost)
od 2009-03-01
Health & Medicine (ProQuest)
od 1997-01-01
- MeSH
- alkaloidy * chemie izolace a purifikace farmakologie MeSH
- apoptóza účinky léků MeSH
- Berberis chemie MeSH
- buňky Hep G2 MeSH
- buňky HT-29 MeSH
- cytotoxiny * chemie izolace a purifikace farmakologie MeSH
- fytogenní protinádorové látky * chemie izolace a purifikace farmakologie MeSH
- G1 fáze účinky léků MeSH
- HeLa buňky MeSH
- Jurkat buňky MeSH
- leukemie farmakoterapie metabolismus patologie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- screeningové testy protinádorových léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články 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.
Citace poskytuje Crossref.org
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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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