Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell
Transitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to adva...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00203/full |
| _version_ | 1819047336278491136 |
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| author | Julieti Huch Buss Karine Rech Begnini Franciele Aline Bruinsmann Taíse Ceolin Mariana Souza Sonego Mariana Souza Sonego Adriana Raffin Pohlmann Adriana Raffin Pohlmann Sílvia Stanisçuaski Guterres Tiago Collares Tiago Collares Fabiana Kömmling Seixas Fabiana Kömmling Seixas |
| author_facet | Julieti Huch Buss Karine Rech Begnini Franciele Aline Bruinsmann Taíse Ceolin Mariana Souza Sonego Mariana Souza Sonego Adriana Raffin Pohlmann Adriana Raffin Pohlmann Sílvia Stanisçuaski Guterres Tiago Collares Tiago Collares Fabiana Kömmling Seixas Fabiana Kömmling Seixas |
| author_sort | Julieti Huch Buss |
| collection | DOAJ |
| description | Transitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to advanced stage tumors. Lapatinib is an important alternative to treat tumors that presents this phenotype due to its ability to inhibit tyrosine kinase residues associated with HER1 and HER2 receptors. This study evaluated the cytotoxicity induced by LAP-loaded nanocapsules (NC-LAP) compared to LAP in HER-positive bladder cancer cell. The cytotoxicity induced by NC-LAP was evaluated through flow cytometry, clonogenic assay and RT-PCR. NC-LAP at 5 μM reduced the cell viability and was able to induce G0/G1 cell cycle arrest with up-regulation of p21. Moreover, NC-LAP treatment presented significantly higher apoptotic rates than untreated cells and cells incubated with drug-unloaded nanocapsules (NC) and an increase in Bax/Bcl-2 ratio was observed in T24 cell line. Furthermore, clonogenic assay demonstrated that NC-LAP treatment eliminated almost all cells with clonogenic capacity. In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype. |
| first_indexed | 2024-12-21T10:58:44Z |
| format | Article |
| id | doaj.art-eadacd007c8b46b586c125596b808943 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T10:58:44Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-eadacd007c8b46b586c125596b8089432022-12-21T19:06:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-04-01910.3389/fonc.2019.00203439278Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer CellJulieti Huch Buss0Karine Rech Begnini1Franciele Aline Bruinsmann2Taíse Ceolin3Mariana Souza Sonego4Mariana Souza Sonego5Adriana Raffin Pohlmann6Adriana Raffin Pohlmann7Sílvia Stanisçuaski Guterres8Tiago Collares9Tiago Collares10Fabiana Kömmling Seixas11Fabiana Kömmling Seixas12Molecular and Cellular Oncology Research Group, Laboratory of Cancer Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilMolecular and Cellular Oncology Research Group, Laboratory of Cancer Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilPharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, BrazilPharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, BrazilMolecular and Cellular Oncology Research Group, Laboratory of Cancer Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilPostgraduate Program in Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilPharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, BrazilInstitute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, BrazilPharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, BrazilMolecular and Cellular Oncology Research Group, Laboratory of Cancer Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilPostgraduate Program in Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilMolecular and Cellular Oncology Research Group, Laboratory of Cancer Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilPostgraduate Program in Biotechnology, Technology Development Center, Federal University of Pelotas, Pelotas, BrazilTransitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to advanced stage tumors. Lapatinib is an important alternative to treat tumors that presents this phenotype due to its ability to inhibit tyrosine kinase residues associated with HER1 and HER2 receptors. This study evaluated the cytotoxicity induced by LAP-loaded nanocapsules (NC-LAP) compared to LAP in HER-positive bladder cancer cell. The cytotoxicity induced by NC-LAP was evaluated through flow cytometry, clonogenic assay and RT-PCR. NC-LAP at 5 μM reduced the cell viability and was able to induce G0/G1 cell cycle arrest with up-regulation of p21. Moreover, NC-LAP treatment presented significantly higher apoptotic rates than untreated cells and cells incubated with drug-unloaded nanocapsules (NC) and an increase in Bax/Bcl-2 ratio was observed in T24 cell line. Furthermore, clonogenic assay demonstrated that NC-LAP treatment eliminated almost all cells with clonogenic capacity. In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype.https://www.frontiersin.org/article/10.3389/fonc.2019.00203/fullbladder cancerher-positiveepidermal growth factor receptor (EGFR)tyrosine kinase inhibitornanocapsuleslapatinib |
| spellingShingle | Julieti Huch Buss Karine Rech Begnini Franciele Aline Bruinsmann Taíse Ceolin Mariana Souza Sonego Mariana Souza Sonego Adriana Raffin Pohlmann Adriana Raffin Pohlmann Sílvia Stanisçuaski Guterres Tiago Collares Tiago Collares Fabiana Kömmling Seixas Fabiana Kömmling Seixas Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell Frontiers in Oncology bladder cancer her-positive epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor nanocapsules lapatinib |
| title | Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell |
| title_full | Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell |
| title_fullStr | Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell |
| title_full_unstemmed | Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell |
| title_short | Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell |
| title_sort | lapatinib loaded nanocapsules enhances antitumoral effect in human bladder cancer cell |
| topic | bladder cancer her-positive epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor nanocapsules lapatinib |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00203/full |
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