ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds
Purpose: ABC proteins transport many substrates such as antibiotics and drugs. Increase of ABCs lead chemoresistance in cancer. In view of this information, in our study, we planned to investigate both PhTAD-substituted dihydropyrrole compound's impact on gene expressions of ABC Transporters...
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| Format: | Article |
| Language: | English |
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Kirsehir Ahi Evran University
2022-04-01
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| Series: | Ahi Evran Medical Journal |
| Subjects: | |
| Online Access: | https://dergipark.org.tr/tr/download/article-file/1638351 |
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| author | Burak YAZGAN Seda MESCİ Maşuk AKŞAHIN Arif AYAR Melek GÜL Tuba YILDIRIM |
| author_facet | Burak YAZGAN Seda MESCİ Maşuk AKŞAHIN Arif AYAR Melek GÜL Tuba YILDIRIM |
| author_sort | Burak YAZGAN |
| collection | DOAJ |
| description | Purpose: ABC proteins transport many substrates such as antibiotics and drugs. Increase of ABCs lead chemoresistance in cancer.
In view of this information, in our study, we planned to investigate both PhTAD-substituted dihydropyrrole compound's impact on
gene expressions of ABC Transporters in the MCF7 cells, and predictive molecular binding sites target on human ABCB1 structure
for these compounds.
Materials and Methods: The mRNA expression levels of ABCB1, ABCC3, ABCC10, ABCC11, and ABCG2 in the MCF-7 cell were
measured by qPCR. Molecular docking assays were realized with both the AutoDock Tools 4.2 and PyMOL 2.4. Also, the interaction
analysis was performed by ProteinsPlus web service.
Results: Our results revealed that CI, CII, CIII, CV, CVIII, and CXII increased ABCB1 while compound CIV, CVI, CVII, CX, CIX,
CXI, CXIII, and CXIV decreased ABCB1. Besides, CI, CIV, CVI, and CVIII upregulate ABCC3, although CVII, CX, CXII, CXIII,
and CXIV downregulate ABCC3. Moreover, ABCC10 expression is induced by all compounds. Conversely, ABCC11 expression is
reduced by all compounds. Furthermore, CII, CV, and CVI increased ABCG2, while CI, CVII, CVIII, CIX, CX, CXI, CXII, CXIII,
and CXIV decreased ABCG2. Also, ABCB1, ABCC3, ABCC11, and ABCG2 parallelly reduced by CVII, CIX, CX, CXI, CXIII, and
CXIV. Also, the molecular docking calculation results of CXI and CXIV with high binding energy have shown that tightly modulated
ABCB1. Especially, these compounds interact with many hydrogen bonding and hydrophobic site on ABCB1.
Conclusion: Our findings indicate that the PhTAD-substituted dihydropyrol containing molecules affect ABC transporters as a potential regulator of cancer chemoresistance. |
| first_indexed | 2024-04-10T10:41:04Z |
| format | Article |
| id | doaj.art-5dd289eaf318407fa0f7c510a8517957 |
| institution | Directory Open Access Journal |
| issn | 2619-9203 |
| language | English |
| last_indexed | 2024-04-10T10:41:04Z |
| publishDate | 2022-04-01 |
| publisher | Kirsehir Ahi Evran University |
| record_format | Article |
| series | Ahi Evran Medical Journal |
| spelling | doaj.art-5dd289eaf318407fa0f7c510a85179572023-02-15T16:20:35ZengKirsehir Ahi Evran UniversityAhi Evran Medical Journal2619-92032022-04-0161778510.46332/aemj.896830ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds Burak YAZGAN0https://orcid.org/0000-0003-0717-7768Seda MESCİ1https://orcid.org/0000-0002-5440-302XMaşuk AKŞAHIN 2https://orcid.org/0000-0002-1282-5072Arif AYAR 3https://orcid.org/0000-0003-0473-4653Melek GÜL4https://orcid.org/0000-0002-0037-1202Tuba YILDIRIM5https://orcid.org/0000-0001-8575-4802Department of Medical Services and Techniques, Sabuncuoğlu Serefeddin Health Services Vocational School, Amasya UniversityHITIT UNIVERSITYAMASYA UNIVERSITYAMASYA UNIVERSITYAMASYA UNIVERSITYAMASYA UNIVERSITYPurpose: ABC proteins transport many substrates such as antibiotics and drugs. Increase of ABCs lead chemoresistance in cancer. In view of this information, in our study, we planned to investigate both PhTAD-substituted dihydropyrrole compound's impact on gene expressions of ABC Transporters in the MCF7 cells, and predictive molecular binding sites target on human ABCB1 structure for these compounds. Materials and Methods: The mRNA expression levels of ABCB1, ABCC3, ABCC10, ABCC11, and ABCG2 in the MCF-7 cell were measured by qPCR. Molecular docking assays were realized with both the AutoDock Tools 4.2 and PyMOL 2.4. Also, the interaction analysis was performed by ProteinsPlus web service. Results: Our results revealed that CI, CII, CIII, CV, CVIII, and CXII increased ABCB1 while compound CIV, CVI, CVII, CX, CIX, CXI, CXIII, and CXIV decreased ABCB1. Besides, CI, CIV, CVI, and CVIII upregulate ABCC3, although CVII, CX, CXII, CXIII, and CXIV downregulate ABCC3. Moreover, ABCC10 expression is induced by all compounds. Conversely, ABCC11 expression is reduced by all compounds. Furthermore, CII, CV, and CVI increased ABCG2, while CI, CVII, CVIII, CIX, CX, CXI, CXII, CXIII, and CXIV decreased ABCG2. Also, ABCB1, ABCC3, ABCC11, and ABCG2 parallelly reduced by CVII, CIX, CX, CXI, CXIII, and CXIV. Also, the molecular docking calculation results of CXI and CXIV with high binding energy have shown that tightly modulated ABCB1. Especially, these compounds interact with many hydrogen bonding and hydrophobic site on ABCB1. Conclusion: Our findings indicate that the PhTAD-substituted dihydropyrol containing molecules affect ABC transporters as a potential regulator of cancer chemoresistance.https://dergipark.org.tr/tr/download/article-file/1638351breast cancerphtad-dihydropyrrolechemoresistanceabcb1abcc3 |
| spellingShingle | Burak YAZGAN Seda MESCİ Maşuk AKŞAHIN Arif AYAR Melek GÜL Tuba YILDIRIM ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds Ahi Evran Medical Journal breast cancer phtad-dihydropyrrole chemoresistance abcb1 abcc3 |
| title | ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds |
| title_full | ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds |
| title_fullStr | ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds |
| title_full_unstemmed | ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds |
| title_short | ATP‐Binding Cassette Transporters Mediated Chemoresistance in MCF-7 Cells: Modulation by PhTAD-Substituted Dihydropyrrole Compounds |
| title_sort | atp binding cassette transporters mediated chemoresistance in mcf 7 cells modulation by phtad substituted dihydropyrrole compounds |
| topic | breast cancer phtad-dihydropyrrole chemoresistance abcb1 abcc3 |
| url | https://dergipark.org.tr/tr/download/article-file/1638351 |
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