Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches
The strong association between POPs and breast cancer in humans has been suggested in various epidemiological studies. However, the interaction of POPs with the ERα protein of breast cancer, and identification of natural and synthetic compounds to inhibit this interaction, is mysterious yet. Consequ...
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MDPI AG
2021-07-01
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| Online Access: | https://www.mdpi.com/2079-7737/10/7/681 |
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| author | Bibi Zainab Zainab Ayaz Umer Rashid Dunia A. Al Farraj Roua M. Alkufeidy Fatmah S. AlQahtany Reem M. Aljowaie Arshad Mehmood Abbasi |
| author_facet | Bibi Zainab Zainab Ayaz Umer Rashid Dunia A. Al Farraj Roua M. Alkufeidy Fatmah S. AlQahtany Reem M. Aljowaie Arshad Mehmood Abbasi |
| author_sort | Bibi Zainab |
| collection | DOAJ |
| description | The strong association between POPs and breast cancer in humans has been suggested in various epidemiological studies. However, the interaction of POPs with the ERα protein of breast cancer, and identification of natural and synthetic compounds to inhibit this interaction, is mysterious yet. Consequently, the present study aimed to explore the interaction between POPs and ERα using the molecular operating environment (MOE) tool and to identify natural and synthetic compounds to inhibit this association through a cluster-based approach. To validate whether our approach could distinguish between active and inactive compounds, a virtual screen (VS) was performed using actives (627 compounds) as positive control and decoys (20,818 compounds) as a negative dataset obtained from DUD-E. Comparatively, short-chain chlorinated paraffins (SCCPs), hexabromocyclododecane (HBCD), and perfluorooctanesulfonyl fluoride (PFOSF) depicted strong interactions with the ERα protein based on the lowest-scoring values of −31.946, −18.916, −17.581 kcal/mol, respectively. Out of 7856 retrieved natural and synthetic compounds, sixty were selected on modularity bases and subsequently docked with ERα. Based on the lowest-scoring values, ZINC08441573, ZINC00664754, ZINC00702695, ZINC00627464, and ZINC08440501 (synthetic compounds), and capsaicin, flavopiridol tectorgenin, and ellagic acid (natural compounds) showed incredible interactions with the active sites of ERα, even more convening and resilient than standard breast cancer drugs Tamoxifen, Arimidex and Letrozole. Our findings confirm the role of POPs in breast cancer progression and suggest that natural and synthetic compounds with high binding affinity could be more efficient and appropriate candidates to treat breast cancer after validation through in vitro and in vivo studies. |
| first_indexed | 2024-03-10T09:44:57Z |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T09:44:57Z |
| publishDate | 2021-07-01 |
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| series | Biology |
| spelling | doaj.art-54298500aa234000861258fc6f4f98292023-11-22T03:16:28ZengMDPI AGBiology2079-77372021-07-0110768110.3390/biology10070681Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network ApproachesBibi Zainab0Zainab Ayaz1Umer Rashid2Dunia A. Al Farraj3Roua M. Alkufeidy4Fatmah S. AlQahtany5Reem M. Aljowaie6Arshad Mehmood Abbasi7Department of Environmental Sciences, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Environmental Sciences, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Chemistry, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Botany and Microbiology, College of Sciences, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Botany and Microbiology, College of Sciences, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Pathology, College of Medicine, King Saud University, Medical City, Riyadh 11495, Saudi ArabiaDepartment of Botany and Microbiology, College of Sciences, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Environmental Sciences, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanThe strong association between POPs and breast cancer in humans has been suggested in various epidemiological studies. However, the interaction of POPs with the ERα protein of breast cancer, and identification of natural and synthetic compounds to inhibit this interaction, is mysterious yet. Consequently, the present study aimed to explore the interaction between POPs and ERα using the molecular operating environment (MOE) tool and to identify natural and synthetic compounds to inhibit this association through a cluster-based approach. To validate whether our approach could distinguish between active and inactive compounds, a virtual screen (VS) was performed using actives (627 compounds) as positive control and decoys (20,818 compounds) as a negative dataset obtained from DUD-E. Comparatively, short-chain chlorinated paraffins (SCCPs), hexabromocyclododecane (HBCD), and perfluorooctanesulfonyl fluoride (PFOSF) depicted strong interactions with the ERα protein based on the lowest-scoring values of −31.946, −18.916, −17.581 kcal/mol, respectively. Out of 7856 retrieved natural and synthetic compounds, sixty were selected on modularity bases and subsequently docked with ERα. Based on the lowest-scoring values, ZINC08441573, ZINC00664754, ZINC00702695, ZINC00627464, and ZINC08440501 (synthetic compounds), and capsaicin, flavopiridol tectorgenin, and ellagic acid (natural compounds) showed incredible interactions with the active sites of ERα, even more convening and resilient than standard breast cancer drugs Tamoxifen, Arimidex and Letrozole. Our findings confirm the role of POPs in breast cancer progression and suggest that natural and synthetic compounds with high binding affinity could be more efficient and appropriate candidates to treat breast cancer after validation through in vitro and in vivo studies.https://www.mdpi.com/2079-7737/10/7/681breast cancerestrogen receptor alphapersistent organic pollutantsdrug-drug interaction networksmolecular docking |
| spellingShingle | Bibi Zainab Zainab Ayaz Umer Rashid Dunia A. Al Farraj Roua M. Alkufeidy Fatmah S. AlQahtany Reem M. Aljowaie Arshad Mehmood Abbasi Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches Biology breast cancer estrogen receptor alpha persistent organic pollutants drug-drug interaction networks molecular docking |
| title | Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches |
| title_full | Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches |
| title_fullStr | Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches |
| title_full_unstemmed | Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches |
| title_short | Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches |
| title_sort | role of persistent organic pollutants in breast cancer progression and identification of estrogen receptor alpha inhibitors using in silico mining and drug drug interaction network approaches |
| topic | breast cancer estrogen receptor alpha persistent organic pollutants drug-drug interaction networks molecular docking |
| url | https://www.mdpi.com/2079-7737/10/7/681 |
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