In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line
Two platinum complexes [Pt(HL3)Cl]·H<sub>2</sub>O (<b>3</b>) and [Pt(HL4)Cl]·H<sub>2</sub>O (<b>4</b>) containing <i>α-</i> and <i>β</i>-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for an...
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MDPI AG
2022-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/10/2013 |
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| author | Leide Laura Figueiredo Maciel Marina Barreto Silva Rafaela Oliveira Moreira Ana Paula Cardoso Christiane Fernandes Adolfo Horn João Carlos de Aquino Almeida Milton Masahiko Kanashiro |
| author_facet | Leide Laura Figueiredo Maciel Marina Barreto Silva Rafaela Oliveira Moreira Ana Paula Cardoso Christiane Fernandes Adolfo Horn João Carlos de Aquino Almeida Milton Masahiko Kanashiro |
| author_sort | Leide Laura Figueiredo Maciel |
| collection | DOAJ |
| description | Two platinum complexes [Pt(HL3)Cl]·H<sub>2</sub>O (<b>3</b>) and [Pt(HL4)Cl]·H<sub>2</sub>O (<b>4</b>) containing <i>α-</i> and <i>β</i>-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for antineoplastic activity. The cytotoxicity activity induced by these platinum(II) compounds against breast cancer (MDA-MB-231 and MCF-7), lung (A549), prostate (PC3), pancreas (BXPC-3), and normal peripheral blood mononuclear (PBMC) cells were evaluated by MTT assay. The cell viability MTT assay showed that complex (<b>4</b>) was more cytotoxic to all cancer cell lines tested and less cytotoxic against human PBMC. Therefore, complex (<b>4</b>) was selected to further investigate the mechanism of cytotoxic effects involved against MDA-MB-231 cell line (human triple-negative breast cancer). Sub-G1 analysis of the cell cycle showed that this complex induces cell death by apoptosis due to the cell loss of DNA content detected in flow cytometry. The cytotoxic effect induced by complex (<b>4</b>) was associated with the capability of the complex to induce mitochondrial membrane depolarization, as well as increase ROS levels and caspase activation, as a result of the activation of both extrinsic and intrinsic apoptosis pathways. Ultrastructural alterations were observed using scanning and transmission electron microscopy (SEM and TEM), such as membrane blebbing, filopodia reduction, empty mitochondrial matrix, and DNA fragmentation. Furthermore, complex (<b>4</b>) was tested in an MDA-MB-231 tumor nodule xenograft murine model and demonstrated a remarkable reduction in tumor size in BALB/c <i>nude</i> mice, when compared to the control animals. |
| first_indexed | 2024-03-09T19:35:34Z |
| format | Article |
| id | doaj.art-654ed0d712f9487c84412439a6d21cb9 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T19:35:34Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-654ed0d712f9487c84412439a6d21cb92023-11-24T01:53:49ZengMDPI AGPharmaceutics1999-49232022-09-011410201310.3390/pharmaceutics14102013In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell LineLeide Laura Figueiredo Maciel0Marina Barreto Silva1Rafaela Oliveira Moreira2Ana Paula Cardoso3Christiane Fernandes4Adolfo Horn5João Carlos de Aquino Almeida6Milton Masahiko Kanashiro7Laboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, RJ, BrazilLaboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, RJ, BrazilCentro Federal de Educação Tecnológica, Nova Friburgo 28635-080, RJ, BrazilDepartamento de Química, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, BrazilDepartamento de Química, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, BrazilDepartamento de Química, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, BrazilLaboratório de Fisiologia e Bioquímica de Microrganismos, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, RJ, BrazilLaboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, RJ, BrazilTwo platinum complexes [Pt(HL3)Cl]·H<sub>2</sub>O (<b>3</b>) and [Pt(HL4)Cl]·H<sub>2</sub>O (<b>4</b>) containing <i>α-</i> and <i>β</i>-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for antineoplastic activity. The cytotoxicity activity induced by these platinum(II) compounds against breast cancer (MDA-MB-231 and MCF-7), lung (A549), prostate (PC3), pancreas (BXPC-3), and normal peripheral blood mononuclear (PBMC) cells were evaluated by MTT assay. The cell viability MTT assay showed that complex (<b>4</b>) was more cytotoxic to all cancer cell lines tested and less cytotoxic against human PBMC. Therefore, complex (<b>4</b>) was selected to further investigate the mechanism of cytotoxic effects involved against MDA-MB-231 cell line (human triple-negative breast cancer). Sub-G1 analysis of the cell cycle showed that this complex induces cell death by apoptosis due to the cell loss of DNA content detected in flow cytometry. The cytotoxic effect induced by complex (<b>4</b>) was associated with the capability of the complex to induce mitochondrial membrane depolarization, as well as increase ROS levels and caspase activation, as a result of the activation of both extrinsic and intrinsic apoptosis pathways. Ultrastructural alterations were observed using scanning and transmission electron microscopy (SEM and TEM), such as membrane blebbing, filopodia reduction, empty mitochondrial matrix, and DNA fragmentation. Furthermore, complex (<b>4</b>) was tested in an MDA-MB-231 tumor nodule xenograft murine model and demonstrated a remarkable reduction in tumor size in BALB/c <i>nude</i> mice, when compared to the control animals.https://www.mdpi.com/1999-4923/14/10/2013breast cancer cellsplatinum(II) complexescytotoxicityapoptosisantitumor |
| spellingShingle | Leide Laura Figueiredo Maciel Marina Barreto Silva Rafaela Oliveira Moreira Ana Paula Cardoso Christiane Fernandes Adolfo Horn João Carlos de Aquino Almeida Milton Masahiko Kanashiro In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line Pharmaceutics breast cancer cells platinum(II) complexes cytotoxicity apoptosis antitumor |
| title | In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line |
| title_full | In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line |
| title_fullStr | In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line |
| title_full_unstemmed | In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line |
| title_short | In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line |
| title_sort | in vitro and in vivo relevant antineoplastic activity of platinum ii complexes toward triple negative mda mb 231 breast cancer cell line |
| topic | breast cancer cells platinum(II) complexes cytotoxicity apoptosis antitumor |
| url | https://www.mdpi.com/1999-4923/14/10/2013 |
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