The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma
Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with...
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MDPI AG
2023-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/12/1682 |
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| author | Wojciech Placha Piotr Suder Agnieszka Panek Patrycja Bronowicka-Adamska Marta Zarzycka Małgorzata Szczygieł Jacek Zagajewski Monika Weronika Piwowar |
| author_facet | Wojciech Placha Piotr Suder Agnieszka Panek Patrycja Bronowicka-Adamska Marta Zarzycka Małgorzata Szczygieł Jacek Zagajewski Monika Weronika Piwowar |
| author_sort | Wojciech Placha |
| collection | DOAJ |
| description | Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model (<i>Mus musculus</i> SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity. |
| first_indexed | 2024-03-08T20:57:25Z |
| format | Article |
| id | doaj.art-192d7a995bd54ec6ab1156539f82de71 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-08T20:57:25Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-192d7a995bd54ec6ab1156539f82de712023-12-22T13:55:45ZengMDPI AGBiomolecules2218-273X2023-11-011312168210.3390/biom13121682The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human MelanomaWojciech Placha0Piotr Suder1Agnieszka Panek2Patrycja Bronowicka-Adamska3Marta Zarzycka4Małgorzata Szczygieł5Jacek Zagajewski6Monika Weronika Piwowar7Department of Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika 7b St., 31-034 Krakow, PolandDepartment of Analytical Chemistry and Biochemistry, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, 31-007 Krakow, PolandInstitute of Nuclear Physics Polish Academy of Sciences, 31-342 Krakow, PolandDepartment of Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika 7b St., 31-034 Krakow, PolandDepartment of Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika 7b St., 31-034 Krakow, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, 31-007 Krakow, PolandDepartment of Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika 7b St., 31-034 Krakow, PolandDepartment of Bioinformatics and Telemedicine, Faculty of Medicine, Jagiellonian University Medical College, Kopernika 7e St., 31-034 Krakow, PolandDespite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model (<i>Mus musculus</i> SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity.https://www.mdpi.com/2218-273X/13/12/1682glycoprotein Phydrophobic statinsdocetaxelmultidrug resistancemelanoma |
| spellingShingle | Wojciech Placha Piotr Suder Agnieszka Panek Patrycja Bronowicka-Adamska Marta Zarzycka Małgorzata Szczygieł Jacek Zagajewski Monika Weronika Piwowar The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma Biomolecules glycoprotein P hydrophobic statins docetaxel multidrug resistance melanoma |
| title | The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma |
| title_full | The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma |
| title_fullStr | The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma |
| title_full_unstemmed | The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma |
| title_short | The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma |
| title_sort | blocking of drug resistance channels by selected hydrophobic statins in chemoresistance human melanoma |
| topic | glycoprotein P hydrophobic statins docetaxel multidrug resistance melanoma |
| url | https://www.mdpi.com/2218-273X/13/12/1682 |
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