Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells
Four new variants of L1210 cells resistant to endoplasmic reticulum (ER) stressors, tunicamycin (S<sub>Tun</sub>), thapsigargin (S<sub>Thap</sub>), bortezomib (S<sub>Bor</sub>), and MG-132 (S<sub>MG-132</sub>), were developed via an 18-month periodic c...
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/11/2517 |
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| author | Martin Cagala Lucia Pavlikova Mario Seres Karolina Kadlecikova Albert Breier Zdena Sulova |
| author_facet | Martin Cagala Lucia Pavlikova Mario Seres Karolina Kadlecikova Albert Breier Zdena Sulova |
| author_sort | Martin Cagala |
| collection | DOAJ |
| description | Four new variants of L1210 cells resistant to endoplasmic reticulum (ER) stressors, tunicamycin (S<sub>Tun</sub>), thapsigargin (S<sub>Thap</sub>), bortezomib (S<sub>Bor</sub>), and MG-132 (S<sub>MG-132</sub>), were developed via an 18-month periodic cultivation in culture medium with a gradual increase in substance concentration. Multidrug resistance was generated for S<sub>Tun</sub> (to tunicamycin, bortezomib and MG-132), S<sub>Thap</sub> (to tunicamycin, thapsigargin and MG-132), S<sub>Bor</sub> (to bortezomib and MG-132), and S<sub>MG-132</sub> (to bortezomib and MG-132). These cells were compared to the original L1210 cells and another two variants, which expressed P-gp due to induction with vincristine or transfection with the gene encoding P-gp, in terms of the following properties: sensitivity to either vincristine or the ER stressors listed above, proliferative activity, expression of resistance markers and proteins involved in the ER stress response, and proteasome activity. The resistance of the new cell variants to ER stressors was accompanied by a decreased proliferation rate and increased proteasome activity. The most consistent change in protein expression was the elevation of GRP78/BiP at the mRNA and protein levels in all resistant variants of L1210 cells. In conclusion, the mechanisms of resistance to these stressors have certain common features, but there are also specific differences. |
| first_indexed | 2024-03-10T19:33:09Z |
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| id | doaj.art-d9fa5abe9d1044b083e7e789b49194e5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:33:09Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d9fa5abe9d1044b083e7e789b49194e52023-11-20T02:01:47ZengMDPI AGMolecules1420-30492020-05-012511251710.3390/molecules25112517Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 CellsMartin Cagala0Lucia Pavlikova1Mario Seres2Karolina Kadlecikova3Albert Breier4Zdena Sulova5Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, SlovakiaInstitute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, SlovakiaInstitute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, SlovakiaInstitute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, 81237 Bratislava, SlovakiaInstitute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, SlovakiaInstitute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, SlovakiaFour new variants of L1210 cells resistant to endoplasmic reticulum (ER) stressors, tunicamycin (S<sub>Tun</sub>), thapsigargin (S<sub>Thap</sub>), bortezomib (S<sub>Bor</sub>), and MG-132 (S<sub>MG-132</sub>), were developed via an 18-month periodic cultivation in culture medium with a gradual increase in substance concentration. Multidrug resistance was generated for S<sub>Tun</sub> (to tunicamycin, bortezomib and MG-132), S<sub>Thap</sub> (to tunicamycin, thapsigargin and MG-132), S<sub>Bor</sub> (to bortezomib and MG-132), and S<sub>MG-132</sub> (to bortezomib and MG-132). These cells were compared to the original L1210 cells and another two variants, which expressed P-gp due to induction with vincristine or transfection with the gene encoding P-gp, in terms of the following properties: sensitivity to either vincristine or the ER stressors listed above, proliferative activity, expression of resistance markers and proteins involved in the ER stress response, and proteasome activity. The resistance of the new cell variants to ER stressors was accompanied by a decreased proliferation rate and increased proteasome activity. The most consistent change in protein expression was the elevation of GRP78/BiP at the mRNA and protein levels in all resistant variants of L1210 cells. In conclusion, the mechanisms of resistance to these stressors have certain common features, but there are also specific differences.https://www.mdpi.com/1420-3049/25/11/2517endoplasmic reticulum stressmultiple drug resistanceL1210 cellstunicamycinthapsigarginbortezomib |
| spellingShingle | Martin Cagala Lucia Pavlikova Mario Seres Karolina Kadlecikova Albert Breier Zdena Sulova Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells Molecules endoplasmic reticulum stress multiple drug resistance L1210 cells tunicamycin thapsigargin bortezomib |
| title | Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells |
| title_full | Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells |
| title_fullStr | Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells |
| title_full_unstemmed | Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells |
| title_short | Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells |
| title_sort | development of resistance to endoplasmic reticulum stress inducing agents in mouse leukemic l1210 cells |
| topic | endoplasmic reticulum stress multiple drug resistance L1210 cells tunicamycin thapsigargin bortezomib |
| url | https://www.mdpi.com/1420-3049/25/11/2517 |
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