XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells
Cisplatin is an election drug widely used in clinic for the treatment of advanced gastric cancer. However, the heterogeneity of the gastric tumors and its resistance to the drugs, make in some cases the response very low and the prognosis unpredictable. In this manuscript we aim to find the molecula...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-10-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01197/full |
| _version_ | 1818542835508445184 |
|---|---|
| author | Natalia Pajuelo-Lozano Natalia Pajuelo-Lozano Jone Bargiela-Iparraguirre Gemma Dominguez Adoracion G. Quiroga Rosario Perona Rosario Perona Isabel Sanchez-Perez Isabel Sanchez-Perez Isabel Sanchez-Perez Isabel Sanchez-Perez |
| author_facet | Natalia Pajuelo-Lozano Natalia Pajuelo-Lozano Jone Bargiela-Iparraguirre Gemma Dominguez Adoracion G. Quiroga Rosario Perona Rosario Perona Isabel Sanchez-Perez Isabel Sanchez-Perez Isabel Sanchez-Perez Isabel Sanchez-Perez |
| author_sort | Natalia Pajuelo-Lozano |
| collection | DOAJ |
| description | Cisplatin is an election drug widely used in clinic for the treatment of advanced gastric cancer. However, the heterogeneity of the gastric tumors and its resistance to the drugs, make in some cases the response very low and the prognosis unpredictable. In this manuscript we aim to find the molecular processes involved in cisplatin-induced apoptosis in two gastric cancer cell lines with different sensitivity to the treatment: AGS and MKN45. The apoptosis induction is higher in MKN45 than in AGS cells in response to CDDP. The intrinsic apoptotic pathway study revealed that MKN45 cells undergo degradation of Mcl-1 together with an increase of Bid and Bad levels, which results in sensitivity to CDDP. In addition, DNA repair NER pathway is impair in MKN45 cells due to low levels of XPC and the absence of translocation of XPA and XPD to the nucleus after stimuli. Altogether, these results suggest that NER and Bcl-2 protein family proteins are potential targets to improve the response to cisplatin treatment. |
| first_indexed | 2024-12-11T22:27:22Z |
| format | Article |
| id | doaj.art-183498ec101d46c38fa7cbbf5607ad98 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T22:27:22Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-183498ec101d46c38fa7cbbf5607ad982022-12-22T00:48:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-10-01910.3389/fphar.2018.01197411910XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer CellsNatalia Pajuelo-Lozano0Natalia Pajuelo-Lozano1Jone Bargiela-Iparraguirre2Gemma Dominguez3Adoracion G. Quiroga4Rosario Perona5Rosario Perona6Isabel Sanchez-Perez7Isabel Sanchez-Perez8Isabel Sanchez-Perez9Isabel Sanchez-Perez10Departamento de Bioquímica, Facultad de Medicina, Instituto de Investigaciones Biomédicas de Madrid, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainInstituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainDepartamento de Bioquímica, Facultad de Medicina, Instituto de Investigaciones Biomédicas de Madrid, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Instituto de Investigaciones Biomédicas de Madrid, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainDepartamento de Quimica Inorganica, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, SpainInstituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainCIBER of Rare Diseases, Valencia, SpainDepartamento de Bioquímica, Facultad de Medicina, Instituto de Investigaciones Biomédicas de Madrid, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainInstituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas – Universidad Autónoma de Madrid, Madrid, SpainCIBER of Rare Diseases, Valencia, SpainUnidad Asociada de Biomedicina, University of Castilla–La Mancha, Consejo Superior de Investigaciones Científicas, Albacete, SpainCisplatin is an election drug widely used in clinic for the treatment of advanced gastric cancer. However, the heterogeneity of the gastric tumors and its resistance to the drugs, make in some cases the response very low and the prognosis unpredictable. In this manuscript we aim to find the molecular processes involved in cisplatin-induced apoptosis in two gastric cancer cell lines with different sensitivity to the treatment: AGS and MKN45. The apoptosis induction is higher in MKN45 than in AGS cells in response to CDDP. The intrinsic apoptotic pathway study revealed that MKN45 cells undergo degradation of Mcl-1 together with an increase of Bid and Bad levels, which results in sensitivity to CDDP. In addition, DNA repair NER pathway is impair in MKN45 cells due to low levels of XPC and the absence of translocation of XPA and XPD to the nucleus after stimuli. Altogether, these results suggest that NER and Bcl-2 protein family proteins are potential targets to improve the response to cisplatin treatment.https://www.frontiersin.org/article/10.3389/fphar.2018.01197/fullgastric cancerapoptosiscisplatinNER repairBcl-2 family |
| spellingShingle | Natalia Pajuelo-Lozano Natalia Pajuelo-Lozano Jone Bargiela-Iparraguirre Gemma Dominguez Adoracion G. Quiroga Rosario Perona Rosario Perona Isabel Sanchez-Perez Isabel Sanchez-Perez Isabel Sanchez-Perez Isabel Sanchez-Perez XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells Frontiers in Pharmacology gastric cancer apoptosis cisplatin NER repair Bcl-2 family |
| title | XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells |
| title_full | XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells |
| title_fullStr | XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells |
| title_full_unstemmed | XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells |
| title_short | XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells |
| title_sort | xpa xpc and xpd modulate sensitivity in gastric cisplatin resistance cancer cells |
| topic | gastric cancer apoptosis cisplatin NER repair Bcl-2 family |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01197/full |
| work_keys_str_mv | AT nataliapajuelolozano xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT nataliapajuelolozano xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT jonebargielaiparraguirre xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT gemmadominguez xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT adoraciongquiroga xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT rosarioperona xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT rosarioperona xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT isabelsanchezperez xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT isabelsanchezperez xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT isabelsanchezperez xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells AT isabelsanchezperez xpaxpcandxpdmodulatesensitivityingastriccisplatinresistancecancercells |