Analyzing the role of phytochemicals in targeting drug transporter protein ABCC6 using molecular docking and molecular dynamics simulations

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks hormonal receptors. This reduces the therapeutic options for TNBC patients creating more focus on chemotherapy. Drug resistance has posed as a major hurdle in treating TNBC patients. Deregulation of drug transporter proteins is one of major factors that cause resistance to chemotherapeutic drugs. In this study, ABCC6 a drug transporter protein that is found dysregulated in several resistant cancer cells has been docked with natural compounds or phytochemicals with known anti-cancer activities. Subtrifloralactone G, a withanolide extracted from Deprea subtriflora is found to show highest binding energy with ABCC6 protein. Molecular dynamics simulations further prove the stability of the ABCC6 protein- Subtrifloralactone G ligand complex. ADMET analysis shows that phytochemical Subtrifloralactone G can be used as an anti-cancer therapeutic drug in treating resistant cancer cells. The study mainly focuses on the role of phytochemicals in treating resistant TNBC cells.

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Faculty Opinions recommendation of The mechano-sensing role of the unique SH3 insertion in plakin domains revealed by Molecular Dynamics simulations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.731190888.793568887 ◽

2019 ◽

Author(s):

Kathleen J Green

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Dynamics Simulations

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Exploring secondary interactions and the role of temperature in moisture-contaminated polymer networks through molecular simulations

Soft Matter ◽

10.1039/d0sm02009e ◽

2021 ◽

Vol 17 (10) ◽

pp. 2942-2956

Author(s):

Rishabh D. Guha ◽

Ogheneovo Idolor ◽

Katherine Berkowitz ◽

Melissa Pasquinelli ◽

Landon R. Grace

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Temperature Variation ◽

Polymer Networks ◽

Molecular Simulations ◽

Effect Of Temperature ◽

Secondary Interactions ◽

Dynamics Simulations ◽

Secondary Bonding

We investigated the effect of temperature variation on the secondary bonding interactions between absorbed moisture and epoxies with different morphologies using molecular dynamics simulations.

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Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis

Human & Experimental Toxicology ◽

10.1177/09603271211021476 ◽

2021 ◽

pp. 096032712110214

Author(s):

Yansong Chen ◽

Ye Tian ◽

Gongsheng Jin ◽

Zhen Cui ◽

Wei Guo ◽

...

Keyword(s):

Breast Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Glutamine Metabolism ◽

Down Regulation ◽

Anti Cancer ◽

Induced Apoptosis ◽

Glutamine Uptake

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

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Molecular insights on poly(N-isopropylacrylamide) coil-to-globule transition induced by pressure

Physical Chemistry Chemical Physics ◽

10.1039/d0cp06452a ◽

2021 ◽

Vol 23 (10) ◽

pp. 5984-5991

Author(s):

Letizia Tavagnacco ◽

Ester Chiessi ◽

Emanuela Zaccarelli

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Polymer Chain ◽

Linear Polymer ◽

Dynamics Simulations ◽

Linear Polymer Chain

By using extensive all-atom molecular dynamics simulations of an atactic linear polymer chain, we unveil the role of pressure in the coil-to-globule transition of poly(N-isopropylacrylamide) (PNIPAM).

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