A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel
<b>Background/Objectives</b>: Triple-negative breast cancer (TNBC) is the most challenging molecular subtype of breast cancer (BC) in clinical practice, associated with a worse prognosis due to limited treatment strategies and its insensitivity to conventional drugs. Zinc is an important...
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2024-12-01
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| author | Raiane Aparecida dos Santos Machado Raoni Pais Siqueira Fernanda Cardoso da Silva André Carlos Pereira de Matos Dayanne Silva Borges Gislaine Gonçalves Rocha Thais Cristina Prado de Souza Rafael Aparecido Carvalho Souza Clayton Rodrigues de Oliveira Antônio G. Ferreira Pedro Ivo da Silva Maia Victor Marcelo Deflon Carolina Gonçalves Oliveira Thaise Gonçalves Araújo |
| author_facet | Raiane Aparecida dos Santos Machado Raoni Pais Siqueira Fernanda Cardoso da Silva André Carlos Pereira de Matos Dayanne Silva Borges Gislaine Gonçalves Rocha Thais Cristina Prado de Souza Rafael Aparecido Carvalho Souza Clayton Rodrigues de Oliveira Antônio G. Ferreira Pedro Ivo da Silva Maia Victor Marcelo Deflon Carolina Gonçalves Oliveira Thaise Gonçalves Araújo |
| author_sort | Raiane Aparecida dos Santos Machado |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Triple-negative breast cancer (TNBC) is the most challenging molecular subtype of breast cancer (BC) in clinical practice, associated with a worse prognosis due to limited treatment strategies and its insensitivity to conventional drugs. Zinc is an important trace element for homeostasis, and its Schiff base metal complexes have shown promise in treating advanced tumors. In this study, four new heteroleptic Zn(II) complexes (<b>1</b>–<b>4</b>) with Schiff bases were synthesized, characterized, and evaluated for their activity in BC cells. <b>Methods</b>: Compounds were synthesized, characterized, and their crystal structures were determined. Biological activity was assessed using MTT, clonogenic, scratch wound healing, caspase 3 and 8 activity, qPCR, and chemosensitization assays. <b>Results</b>: The complexes exhibited cytotoxicity against MCF-7 (luminal BC), MDA-MB-453 (HER2-positive BC), and MDA-MB-231 (TNBC) cell lines, with IC<sub>50</sub> values ranging from 0.01 to 20 µM. Complex <b>4</b> showed reduced cytotoxicity toward non-tumor cell lines. This, complexation with Zn(II) increased the cytotoxicity of the ligands, a trend not observed for complexes <b>1</b>–<b>3</b>. Due to its favorable profile, complex <b>4</b> was selected for further assays, in which it inhibited colony formation and the cell migration of TNBC cells in a dose-dependent manner. Furthermore, this compound induced cell death independently of caspases, decreasing the activity of caspase 8. Interestingly, complex <b>4</b> sensitized TBNC cells to doxorubicin and paclitaxel, possibly modulating the epithelial–mesenchymal transition mechanism, as evidenced by increased <i>CDH1</i> expression. <b>Conclusions</b>: Results suggest the potential of complex <b>4</b> in sensitizing aggressive BC cells to chemotherapy, proving to be a promising alternative in cases of therapeutic failure. |
| format | Article |
| id | doaj-art-6f82b7b5a5e4439dbea84e34743d10dc |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-6f82b7b5a5e4439dbea84e34743d10dc2025-08-20T02:57:28ZengMDPI AGPharmaceutics1999-49232024-12-011612161010.3390/pharmaceutics16121610A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and PaclitaxelRaiane Aparecida dos Santos Machado0Raoni Pais Siqueira1Fernanda Cardoso da Silva2André Carlos Pereira de Matos3Dayanne Silva Borges4Gislaine Gonçalves Rocha5Thais Cristina Prado de Souza6Rafael Aparecido Carvalho Souza7Clayton Rodrigues de Oliveira8Antônio G. Ferreira9Pedro Ivo da Silva Maia10Victor Marcelo Deflon11Carolina Gonçalves Oliveira12Thaise Gonçalves Araújo13Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, BrazilLaboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, BrazilLaboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, BrazilLaboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, BrazilLaboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, BrazilLaboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, BrazilInstitute of Chemistry, Federal University of Uberlândia, Uberlândia 38400-902, MG, BrazilInstitute of Chemistry, Federal University of Uberlândia, Uberlândia 38400-902, MG, BrazilDepartment of Chemistry, Federal University of São Carlos, Rodovia Washington Luís, km 235, São Carlos 13565-905, SP, BrazilDepartment of Chemistry, Federal University of São Carlos, Rodovia Washington Luís, km 235, São Carlos 13565-905, SP, BrazilBioactive Compounds Development Research Group, Federal University of Triangulo Mineiro, Av. Dr. Randolfo Borges 1400, Uberaba 38025-440, MG, BrazilSão Carlos Institute of Chemistry, University of São Paulo, São Carlos 13560-970, SP, BrazilInstitute of Chemistry, Federal University of Uberlândia, Uberlândia 38400-902, MG, BrazilLaboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlândia, Patos de Minas 38700-002, MG, Brazil<b>Background/Objectives</b>: Triple-negative breast cancer (TNBC) is the most challenging molecular subtype of breast cancer (BC) in clinical practice, associated with a worse prognosis due to limited treatment strategies and its insensitivity to conventional drugs. Zinc is an important trace element for homeostasis, and its Schiff base metal complexes have shown promise in treating advanced tumors. In this study, four new heteroleptic Zn(II) complexes (<b>1</b>–<b>4</b>) with Schiff bases were synthesized, characterized, and evaluated for their activity in BC cells. <b>Methods</b>: Compounds were synthesized, characterized, and their crystal structures were determined. Biological activity was assessed using MTT, clonogenic, scratch wound healing, caspase 3 and 8 activity, qPCR, and chemosensitization assays. <b>Results</b>: The complexes exhibited cytotoxicity against MCF-7 (luminal BC), MDA-MB-453 (HER2-positive BC), and MDA-MB-231 (TNBC) cell lines, with IC<sub>50</sub> values ranging from 0.01 to 20 µM. Complex <b>4</b> showed reduced cytotoxicity toward non-tumor cell lines. This, complexation with Zn(II) increased the cytotoxicity of the ligands, a trend not observed for complexes <b>1</b>–<b>3</b>. Due to its favorable profile, complex <b>4</b> was selected for further assays, in which it inhibited colony formation and the cell migration of TNBC cells in a dose-dependent manner. Furthermore, this compound induced cell death independently of caspases, decreasing the activity of caspase 8. Interestingly, complex <b>4</b> sensitized TBNC cells to doxorubicin and paclitaxel, possibly modulating the epithelial–mesenchymal transition mechanism, as evidenced by increased <i>CDH1</i> expression. <b>Conclusions</b>: Results suggest the potential of complex <b>4</b> in sensitizing aggressive BC cells to chemotherapy, proving to be a promising alternative in cases of therapeutic failure.https://www.mdpi.com/1999-4923/16/12/1610Zinc(II)MDA-MB-231breast cancerchemotherapy |
| spellingShingle | Raiane Aparecida dos Santos Machado Raoni Pais Siqueira Fernanda Cardoso da Silva André Carlos Pereira de Matos Dayanne Silva Borges Gislaine Gonçalves Rocha Thais Cristina Prado de Souza Rafael Aparecido Carvalho Souza Clayton Rodrigues de Oliveira Antônio G. Ferreira Pedro Ivo da Silva Maia Victor Marcelo Deflon Carolina Gonçalves Oliveira Thaise Gonçalves Araújo A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel Pharmaceutics Zinc(II) MDA-MB-231 breast cancer chemotherapy |
| title | A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel |
| title_full | A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel |
| title_fullStr | A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel |
| title_full_unstemmed | A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel |
| title_short | A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel |
| title_sort | new heteroleptic zn ii complex with schiff bases sensitizes triple negative breast cancer cells to doxorubicin and paclitaxel |
| topic | Zinc(II) MDA-MB-231 breast cancer chemotherapy |
| url | https://www.mdpi.com/1999-4923/16/12/1610 |
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