Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents
In this study, we evaluated the cytotoxic activity and antiproliferative potency of novel octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives ( 1 – 7 ) in MCF-7 and MDA-MB-231 breast cancer cell lines. Annexin V binding assay and disruption of the mitochondrial potential were performed to deter...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2017-05-01
|
| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317701641 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850053321158557696 |
|---|---|
| author | Agnieszka Gornowicz Natalia Pawłowska Anna Czajkowska Robert Czarnomysy Anna Bielawska Krzysztof Bielawski Olga Michalak Olga Staszewska-Krajewska Zbigniew Kałuża |
| author_facet | Agnieszka Gornowicz Natalia Pawłowska Anna Czajkowska Robert Czarnomysy Anna Bielawska Krzysztof Bielawski Olga Michalak Olga Staszewska-Krajewska Zbigniew Kałuża |
| author_sort | Agnieszka Gornowicz |
| collection | DOAJ |
| description | In this study, we evaluated the cytotoxic activity and antiproliferative potency of novel octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives ( 1 – 7 ) in MCF-7 and MDA-MB-231 breast cancer cell lines. Annexin V binding assay and disruption of the mitochondrial potential were performed to determine apoptosis. The activity of caspases 3, 8, 9, and 10 was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The results from experiments were compared with effects obtained after incubation in the presence of camptothecin and etoposide. Our study demonstrated that the most active compounds in both analyzed breast cancer cell lines were compounds 3 and 4 . We also observed that all compounds induced apoptosis. We demonstrated the higher activity of caspases 3, 8, 9, and 10, which confirmed that induction of apoptosis is associated with external and internal cell death pathway. Our study revealed that the novel compounds in group of diisoquinoline derivatives are promising candidates in anticancer treatment by activation of both extrinsic and intrinsic apoptotic pathways. |
| format | Article |
| id | doaj-art-7008c7bcda554d599ec71ea88eb0e4ba |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-7008c7bcda554d599ec71ea88eb0e4ba2025-08-20T02:52:34ZengSAGE PublishingTumor Biology1423-03802017-05-013910.1177/1010428317701641Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agentsAgnieszka Gornowicz0Natalia Pawłowska1Anna Czajkowska2Robert Czarnomysy3Anna Bielawska4Krzysztof Bielawski5Olga Michalak6Olga Staszewska-Krajewska7Zbigniew Kałuża8Department of Biotechnology, Medical University of Bialystok, Bialystok, PolandDepartment of Synthesis and Technology of Drugs, Medical University of Bialystok, Bialystok, PolandDepartment of Biotechnology, Medical University of Bialystok, Bialystok, PolandDepartment of Synthesis and Technology of Drugs, Medical University of Bialystok, Bialystok, PolandDepartment of Biotechnology, Medical University of Bialystok, Bialystok, PolandDepartment of Synthesis and Technology of Drugs, Medical University of Bialystok, Bialystok, PolandInstitute of Organic Chemistry, Polish Academy of Sciences, Warsaw, PolandInstitute of Organic Chemistry, Polish Academy of Sciences, Warsaw, PolandInstitute of Organic Chemistry, Polish Academy of Sciences, Warsaw, PolandIn this study, we evaluated the cytotoxic activity and antiproliferative potency of novel octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives ( 1 – 7 ) in MCF-7 and MDA-MB-231 breast cancer cell lines. Annexin V binding assay and disruption of the mitochondrial potential were performed to determine apoptosis. The activity of caspases 3, 8, 9, and 10 was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The results from experiments were compared with effects obtained after incubation in the presence of camptothecin and etoposide. Our study demonstrated that the most active compounds in both analyzed breast cancer cell lines were compounds 3 and 4 . We also observed that all compounds induced apoptosis. We demonstrated the higher activity of caspases 3, 8, 9, and 10, which confirmed that induction of apoptosis is associated with external and internal cell death pathway. Our study revealed that the novel compounds in group of diisoquinoline derivatives are promising candidates in anticancer treatment by activation of both extrinsic and intrinsic apoptotic pathways.https://doi.org/10.1177/1010428317701641 |
| spellingShingle | Agnieszka Gornowicz Natalia Pawłowska Anna Czajkowska Robert Czarnomysy Anna Bielawska Krzysztof Bielawski Olga Michalak Olga Staszewska-Krajewska Zbigniew Kałuża Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents Tumor Biology |
| title | Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents |
| title_full | Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents |
| title_fullStr | Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents |
| title_full_unstemmed | Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents |
| title_short | Biological evaluation of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives as potent anticancer agents |
| title_sort | biological evaluation of octahydropyrazin 2 1 a 5 4 a diisoquinoline derivatives as potent anticancer agents |
| url | https://doi.org/10.1177/1010428317701641 |
| work_keys_str_mv | AT agnieszkagornowicz biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT nataliapawłowska biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT annaczajkowska biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT robertczarnomysy biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT annabielawska biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT krzysztofbielawski biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT olgamichalak biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT olgastaszewskakrajewska biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents AT zbigniewkałuza biologicalevaluationofoctahydropyrazin21a54adiisoquinolinederivativesaspotentanticanceragents |