Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells.
Over the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4201456?pdf=render |
| _version_ | 1818249162039230464 |
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| author | Aliny Pereira Lima Flávia Castro Pereira Marcio Aurelio Pinheiro Almeida Francyelli Mariana Santos Mello Wanessa Carvalho Pires Thallita Monteiro Pinto Flávia Karina Delella Sérgio Luis Felisbino Virtudes Moreno Alzir Azevedo Batista Elisângela de Paula Silveira-Lacerda |
| author_facet | Aliny Pereira Lima Flávia Castro Pereira Marcio Aurelio Pinheiro Almeida Francyelli Mariana Santos Mello Wanessa Carvalho Pires Thallita Monteiro Pinto Flávia Karina Delella Sérgio Luis Felisbino Virtudes Moreno Alzir Azevedo Batista Elisângela de Paula Silveira-Lacerda |
| author_sort | Aliny Pereira Lima |
| collection | DOAJ |
| description | Over the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amino acids were studied in vitro to determine their biological activity against sarcoma-180 tumor cells. The cytotoxicity of the complexes was evaluated by an MTT assay, and their mechanism of action was investigated. The results demonstrated that the five complexes inhibited the growth of the S180 tumor cell line, with IC50 values ranging from 22.53 µM to 50.18 µM, and showed low cytotoxicity against normal L929 fibroblast cells. Flow cytometric analysis revealed that the [Ru(gly)(bipy)(dppb)]PF6 complex (2) inhibited the growth of the tumor cells by inducing apoptosis, as evidenced by an increased number of Annexin V-positive cells and G0/G1 phase cell cycle arrest. Further investigation showed that complex 2 caused a loss of mitochondrial membrane potential; activated caspases 3, caspase-8, and caspase-9 and caused a change in the mRNA expression levels of caspase 3, caspase-9 as well as the bax genes. The levels of the pro-apoptotic Bcl-2 family protein Bak were increased. Thus, we demonstrated that ruthenium amino acid complexes are promising drugs against S180 tumor cells, and we recommend further investigations of their role as chemotherapeutic agents for sarcomas. |
| first_indexed | 2024-12-12T15:32:06Z |
| format | Article |
| id | doaj.art-605e60f82f6f417c9bdbaa8c86c44d29 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T15:32:06Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-605e60f82f6f417c9bdbaa8c86c44d292022-12-22T00:20:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10586510.1371/journal.pone.0105865Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells.Aliny Pereira LimaFlávia Castro PereiraMarcio Aurelio Pinheiro AlmeidaFrancyelli Mariana Santos MelloWanessa Carvalho PiresThallita Monteiro PintoFlávia Karina DelellaSérgio Luis FelisbinoVirtudes MorenoAlzir Azevedo BatistaElisângela de Paula Silveira-LacerdaOver the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amino acids were studied in vitro to determine their biological activity against sarcoma-180 tumor cells. The cytotoxicity of the complexes was evaluated by an MTT assay, and their mechanism of action was investigated. The results demonstrated that the five complexes inhibited the growth of the S180 tumor cell line, with IC50 values ranging from 22.53 µM to 50.18 µM, and showed low cytotoxicity against normal L929 fibroblast cells. Flow cytometric analysis revealed that the [Ru(gly)(bipy)(dppb)]PF6 complex (2) inhibited the growth of the tumor cells by inducing apoptosis, as evidenced by an increased number of Annexin V-positive cells and G0/G1 phase cell cycle arrest. Further investigation showed that complex 2 caused a loss of mitochondrial membrane potential; activated caspases 3, caspase-8, and caspase-9 and caused a change in the mRNA expression levels of caspase 3, caspase-9 as well as the bax genes. The levels of the pro-apoptotic Bcl-2 family protein Bak were increased. Thus, we demonstrated that ruthenium amino acid complexes are promising drugs against S180 tumor cells, and we recommend further investigations of their role as chemotherapeutic agents for sarcomas.http://europepmc.org/articles/PMC4201456?pdf=render |
| spellingShingle | Aliny Pereira Lima Flávia Castro Pereira Marcio Aurelio Pinheiro Almeida Francyelli Mariana Santos Mello Wanessa Carvalho Pires Thallita Monteiro Pinto Flávia Karina Delella Sérgio Luis Felisbino Virtudes Moreno Alzir Azevedo Batista Elisângela de Paula Silveira-Lacerda Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. PLoS ONE |
| title | Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. |
| title_full | Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. |
| title_fullStr | Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. |
| title_full_unstemmed | Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. |
| title_short | Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. |
| title_sort | cytoxicity and apoptotic mechanism of ruthenium ii amino acid complexes in sarcoma 180 tumor cells |
| url | http://europepmc.org/articles/PMC4201456?pdf=render |
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