The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches
Abstract Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2. The major goal of this study was to ide...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-023-04198-z |
| _version_ | 1797637150491017216 |
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| author | Rida Sultan Abrar Ahmed Li Wei Hamid Saeed Muhammad Islam Muhammad Ishaq |
| author_facet | Rida Sultan Abrar Ahmed Li Wei Hamid Saeed Muhammad Islam Muhammad Ishaq |
| author_sort | Rida Sultan |
| collection | DOAJ |
| description | Abstract Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2. The major goal of this study was to identify the potential inhibitors of CDK-2 present in Moringa oleifera for treating hormonal receptor positive breast cancers. For this purpose, in silico techniques; molecular docking, MM-GBSA and molecular dynamics simulations were employed to screen Moringa oleifera compounds and their anticancer potential was determined against CDK-2 protein targets. Among 36 compounds of Moringa oleifera reported in literature, chlorogenic acid (1), quercetin (2), ellagic acid (3), niazirin (4), and kaempferol (5) showed good affinity with the target. The interaction of the compounds was visualized using PYMOL software. The profiles of absorption, distribution, metabolism, excretion (ADME) and toxicity were determined using SWISS and ProTox II webservers. The MTT assay was performed in-vitro using MCF-7 cancer cell lines to validate the anticancer potential of Moringa oleifera leaf extract. MTT assay results revealed no significant change in proliferation of Mcf-7 cells following 24 h treatment with fraction A (petroleum ether). However, significant antiproliferative effect was observed at 200 µg/mL dose of fraction B (ethyl acetate) and cell viability was reduced to 40%. In conclusion, the data suggested that all the compounds with highest negative docking score than the reference could be the potential candidates for cyclin dependent kinase-2 (CDK-2) inhibition while ellagic acid, chlorogenic acid and quercetin being the most stable and potent inhibitors to treat estrogen receptor positive breast cancer targeting CDK-2. Moreover, the data suggested that further investigation is required to determine the optimum dose for significant antiproliferative effects using in-vivo models to validate our findings of in-silico analysis. |
| first_indexed | 2024-03-11T12:44:17Z |
| format | Article |
| id | doaj.art-f93741f067be4676b74fe9081dad3cfc |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-03-11T12:44:17Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-f93741f067be4676b74fe9081dad3cfc2023-11-05T12:07:45ZengBMCBMC Complementary Medicine and Therapies2662-76712023-11-0123111710.1186/s12906-023-04198-zThe anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approchesRida Sultan0Abrar Ahmed1Li Wei2Hamid Saeed3Muhammad Islam4Muhammad Ishaq5Faculty of Pharmacy, Punjab University College of Pharmacy, University of the PunjabFaculty of Pharmacy, Punjab University College of Pharmacy, University of the PunjabZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS)Faculty of Pharmacy, Punjab University College of Pharmacy, University of the PunjabFaculty of Pharmacy, Punjab University College of Pharmacy, University of the PunjabInstitute of Social and Cultural Studies, University of the PunjabAbstract Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2. The major goal of this study was to identify the potential inhibitors of CDK-2 present in Moringa oleifera for treating hormonal receptor positive breast cancers. For this purpose, in silico techniques; molecular docking, MM-GBSA and molecular dynamics simulations were employed to screen Moringa oleifera compounds and their anticancer potential was determined against CDK-2 protein targets. Among 36 compounds of Moringa oleifera reported in literature, chlorogenic acid (1), quercetin (2), ellagic acid (3), niazirin (4), and kaempferol (5) showed good affinity with the target. The interaction of the compounds was visualized using PYMOL software. The profiles of absorption, distribution, metabolism, excretion (ADME) and toxicity were determined using SWISS and ProTox II webservers. The MTT assay was performed in-vitro using MCF-7 cancer cell lines to validate the anticancer potential of Moringa oleifera leaf extract. MTT assay results revealed no significant change in proliferation of Mcf-7 cells following 24 h treatment with fraction A (petroleum ether). However, significant antiproliferative effect was observed at 200 µg/mL dose of fraction B (ethyl acetate) and cell viability was reduced to 40%. In conclusion, the data suggested that all the compounds with highest negative docking score than the reference could be the potential candidates for cyclin dependent kinase-2 (CDK-2) inhibition while ellagic acid, chlorogenic acid and quercetin being the most stable and potent inhibitors to treat estrogen receptor positive breast cancer targeting CDK-2. Moreover, the data suggested that further investigation is required to determine the optimum dose for significant antiproliferative effects using in-vivo models to validate our findings of in-silico analysis.https://doi.org/10.1186/s12906-023-04198-zCDK2ER+ Breast cancerMolecular DockingMM-GBSAMolecular Dynamic SimulationsMTT assay |
| spellingShingle | Rida Sultan Abrar Ahmed Li Wei Hamid Saeed Muhammad Islam Muhammad Ishaq The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches BMC Complementary Medicine and Therapies CDK2 ER+ Breast cancer Molecular Docking MM-GBSA Molecular Dynamic Simulations MTT assay |
| title | The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches |
| title_full | The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches |
| title_fullStr | The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches |
| title_full_unstemmed | The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches |
| title_short | The anticancer potential of chemical constituents of Moringa oleifera targeting CDK-2 inhibition in estrogen receptor positive breast cancer using in-silico and in vitro approches |
| title_sort | anticancer potential of chemical constituents of moringa oleifera targeting cdk 2 inhibition in estrogen receptor positive breast cancer using in silico and in vitro approches |
| topic | CDK2 ER+ Breast cancer Molecular Docking MM-GBSA Molecular Dynamic Simulations MTT assay |
| url | https://doi.org/10.1186/s12906-023-04198-z |
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