Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model.
Introduction and objectives: Liver disease causes approximately 1.75 million deaths per year and chronic liver disease (CLD) and is usually detected in advanced stages (cirrhosis or hepatocellular carcinoma) that require partial ablation or transplant. STAT-3 has been identified as a therapeutic tar...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-02-01
|
| Series: | Annals of Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268124001972 |
| _version_ | 1797272516278878208 |
|---|---|
| author | Moises Martinez-Castillo Cristina Piña-Barba Israel A. Núñez-Tapia Marisela Hernandez-Santillan Abigail Hernández-Barragán Gabriela Gutiérrez-Reyes |
| author_facet | Moises Martinez-Castillo Cristina Piña-Barba Israel A. Núñez-Tapia Marisela Hernandez-Santillan Abigail Hernández-Barragán Gabriela Gutiérrez-Reyes |
| author_sort | Moises Martinez-Castillo |
| collection | DOAJ |
| description | Introduction and objectives: Liver disease causes approximately 1.75 million deaths per year and chronic liver disease (CLD) and is usually detected in advanced stages (cirrhosis or hepatocellular carcinoma) that require partial ablation or transplant. STAT-3 has been identified as a therapeutic target in cancer. Moreover, collagen matrix scaffolds (CMS) can be used as carriers of antineoplastic drugs for hepatocellular carcinoma. The objective was to determine the capacity of CMS as vehicle of WP1066 (inhibitor of STAT3) in an in vitro HCC model. Materials and Patients: WP1066 was incubated with HCC cell lines to determine the IC50 by the Resazurin method. After this, the IC50 concentration of WP1066 was added to CMS during 1, 3 and 7 days before the incubation with each HCC cell, then the WP1066 stability was evaluated by mass spectrometry. The pH of the RPMI medium was evaluated in all the experimental conditions using a potentiometer. Whereas the cell viability was compared with untreated cells and CMs without WP1066 by Resazurin method. Results: The IC50 of WP1066 for HEPA 1-6 and HEPG2 was similar 1.54 uM ± 0.07 and 1.68 ± 0.16 uM, respectively. WP1066 showed stability after 7 days of preparation in DMSO. The pH evaluation of RPMI with WP1066, CMS and WP1066+CMS was similar (pH 7.2) at 72 h of incubation. Cell viability of both HHC cell lines was reduced 80% in the combination of CM plus WP1066 (p<0.001), however, CM alone also promotes the reduction of cell viability like WP1066 alone (50%) (p<0.001). Conclusions: Previously, we reported that CM allows the survival and proliferation of mesenchymal stem cells. CM can be used as a vehicle of WP1066; moreover, CM alone or in combination with WP1066 promotes reduction of HCC cell lines. It is possible that hydroxyapatite from CM promotes reduction of cell viability of cancer cells but does not cause negative effects in mesenchymal stem cells. |
| first_indexed | 2024-03-07T14:30:28Z |
| format | Article |
| id | doaj.art-d989a116d45c4e53a0bf06a33e6bd461 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-03-07T14:30:28Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-d989a116d45c4e53a0bf06a33e6bd4612024-03-06T05:25:58ZengElsevierAnnals of Hepatology1665-26812024-02-0129101403Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model.Moises Martinez-Castillo0Cristina Piña-Barba1Israel A. Núñez-Tapia2Marisela Hernandez-Santillan3Abigail Hernández-Barragán4Gabriela Gutiérrez-Reyes5Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina, UNAM, Hospital General de Mexico, Dr. Eduardo LiceagaInstituto de Investigaciones en Materiales, UNAM, Ciudad de MéxicoInstituto de Investigaciones en Materiales, UNAM, Ciudad de MéxicoLaboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina, UNAM, Hospital General de Mexico, Dr. Eduardo LiceagaLaboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina, UNAM, Hospital General de Mexico, Dr. Eduardo LiceagaLaboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina, UNAM, Hospital General de Mexico, Dr. Eduardo LiceagaIntroduction and objectives: Liver disease causes approximately 1.75 million deaths per year and chronic liver disease (CLD) and is usually detected in advanced stages (cirrhosis or hepatocellular carcinoma) that require partial ablation or transplant. STAT-3 has been identified as a therapeutic target in cancer. Moreover, collagen matrix scaffolds (CMS) can be used as carriers of antineoplastic drugs for hepatocellular carcinoma. The objective was to determine the capacity of CMS as vehicle of WP1066 (inhibitor of STAT3) in an in vitro HCC model. Materials and Patients: WP1066 was incubated with HCC cell lines to determine the IC50 by the Resazurin method. After this, the IC50 concentration of WP1066 was added to CMS during 1, 3 and 7 days before the incubation with each HCC cell, then the WP1066 stability was evaluated by mass spectrometry. The pH of the RPMI medium was evaluated in all the experimental conditions using a potentiometer. Whereas the cell viability was compared with untreated cells and CMs without WP1066 by Resazurin method. Results: The IC50 of WP1066 for HEPA 1-6 and HEPG2 was similar 1.54 uM ± 0.07 and 1.68 ± 0.16 uM, respectively. WP1066 showed stability after 7 days of preparation in DMSO. The pH evaluation of RPMI with WP1066, CMS and WP1066+CMS was similar (pH 7.2) at 72 h of incubation. Cell viability of both HHC cell lines was reduced 80% in the combination of CM plus WP1066 (p<0.001), however, CM alone also promotes the reduction of cell viability like WP1066 alone (50%) (p<0.001). Conclusions: Previously, we reported that CM allows the survival and proliferation of mesenchymal stem cells. CM can be used as a vehicle of WP1066; moreover, CM alone or in combination with WP1066 promotes reduction of HCC cell lines. It is possible that hydroxyapatite from CM promotes reduction of cell viability of cancer cells but does not cause negative effects in mesenchymal stem cells.http://www.sciencedirect.com/science/article/pii/S1665268124001972 |
| spellingShingle | Moises Martinez-Castillo Cristina Piña-Barba Israel A. Núñez-Tapia Marisela Hernandez-Santillan Abigail Hernández-Barragán Gabriela Gutiérrez-Reyes Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model. Annals of Hepatology |
| title | Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model. |
| title_full | Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model. |
| title_fullStr | Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model. |
| title_full_unstemmed | Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model. |
| title_short | Collagen matrix scaffold as vehicle of WP1066, STAT-3 inhibitors, in an in vitro hepatocellular model. |
| title_sort | collagen matrix scaffold as vehicle of wp1066 stat 3 inhibitors in an in vitro hepatocellular model |
| url | http://www.sciencedirect.com/science/article/pii/S1665268124001972 |
| work_keys_str_mv | AT moisesmartinezcastillo collagenmatrixscaffoldasvehicleofwp1066stat3inhibitorsinaninvitrohepatocellularmodel AT cristinapinabarba collagenmatrixscaffoldasvehicleofwp1066stat3inhibitorsinaninvitrohepatocellularmodel AT israelanuneztapia collagenmatrixscaffoldasvehicleofwp1066stat3inhibitorsinaninvitrohepatocellularmodel AT mariselahernandezsantillan collagenmatrixscaffoldasvehicleofwp1066stat3inhibitorsinaninvitrohepatocellularmodel AT abigailhernandezbarragan collagenmatrixscaffoldasvehicleofwp1066stat3inhibitorsinaninvitrohepatocellularmodel AT gabrielagutierrezreyes collagenmatrixscaffoldasvehicleofwp1066stat3inhibitorsinaninvitrohepatocellularmodel |