Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells
Multidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P...
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MDPI AG
2020-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/7/1654 |
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| author | Olga Wesołowska Krystyna Michalak Maria Błaszczyk Joseph Molnár Kamila Środa-Pomianek |
| author_facet | Olga Wesołowska Krystyna Michalak Maria Błaszczyk Joseph Molnár Kamila Środa-Pomianek |
| author_sort | Olga Wesołowska |
| collection | DOAJ |
| description | Multidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P-glycoprotein). At the expense of ATP hydrolysis, ABCB1 pumps a diverse range of substrates (including anticancer drugs) out of the cell, thereby reducing their intracellular concentration. In the present study, the ability of two patented disiloxanes (SILA-409 and SILA-421) to reverse drug resistance in human colon adenocarcinoma cell lines LoVo and LoVo/Dx was investigated. It was demonstrated that both compounds in concentrations of 0.5–1 µM strongly increased the sensitivity of LoVo/Dx cells to doxorubicin. By means of an accumulation test in which rhodamine 123 was used as an ABCB1 substrate analogue, both organosilicon compounds were also shown to inhibit ABCB1 transport activity. The intracellular accumulation of doxorubicin was also increased, and more drug entered the cellular nuclei of resistant cells in the presence of the studied compounds. In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells. |
| first_indexed | 2024-03-10T20:41:29Z |
| format | Article |
| id | doaj.art-ed476e311eee48a7855e962b7b458180 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T20:41:29Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ed476e311eee48a7855e962b7b4581802023-11-19T20:39:51ZengMDPI AGMolecules1420-30492020-04-01257165410.3390/molecules25071654Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer CellsOlga Wesołowska0Krystyna Michalak1Maria Błaszczyk2Joseph Molnár3Kamila Środa-Pomianek4Department of Biophysics and Neuroscience, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, 50-367 Wroclaw, PolandInstitute of Medical Microbiology and Immunobiology, University of Szeged, 6720 Szeged, HungaryDepartment of Biophysics and Neuroscience, Wroclaw Medical University, 50-367 Wroclaw, PolandMultidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P-glycoprotein). At the expense of ATP hydrolysis, ABCB1 pumps a diverse range of substrates (including anticancer drugs) out of the cell, thereby reducing their intracellular concentration. In the present study, the ability of two patented disiloxanes (SILA-409 and SILA-421) to reverse drug resistance in human colon adenocarcinoma cell lines LoVo and LoVo/Dx was investigated. It was demonstrated that both compounds in concentrations of 0.5–1 µM strongly increased the sensitivity of LoVo/Dx cells to doxorubicin. By means of an accumulation test in which rhodamine 123 was used as an ABCB1 substrate analogue, both organosilicon compounds were also shown to inhibit ABCB1 transport activity. The intracellular accumulation of doxorubicin was also increased, and more drug entered the cellular nuclei of resistant cells in the presence of the studied compounds. In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells.https://www.mdpi.com/1420-3049/25/7/1654organosilicon compoundsSILA-409 (Alis-409)SILA-421 (Alis-421)multidrug resistance (MDR) reversalABCB1 (P-glycoprotein)colon cancer |
| spellingShingle | Olga Wesołowska Krystyna Michalak Maria Błaszczyk Joseph Molnár Kamila Środa-Pomianek Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells Molecules organosilicon compounds SILA-409 (Alis-409) SILA-421 (Alis-421) multidrug resistance (MDR) reversal ABCB1 (P-glycoprotein) colon cancer |
| title | Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells |
| title_full | Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells |
| title_fullStr | Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells |
| title_full_unstemmed | Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells |
| title_short | Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells |
| title_sort | organosilicon compounds sila 409 and sila 421 as doxorubicin resistance reversing agents in human colon cancer cells |
| topic | organosilicon compounds SILA-409 (Alis-409) SILA-421 (Alis-421) multidrug resistance (MDR) reversal ABCB1 (P-glycoprotein) colon cancer |
| url | https://www.mdpi.com/1420-3049/25/7/1654 |
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