Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico

Doxorubicin chemotherapy has been a strong focus in breast cancer research. Side effects, toxicity and resistance have been extensively studied. One proposed solution to these issues that its combination with deoxyelephantopin. Deoxyelephantopin is known to be toxic in many cancer cells but safe in...

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Main Authors: DANIEL DANIEL, FRENGKI FRENGKI, MUHAMMAD JALALUDDIN, WAHYU EKA SARI, ROSMAIDAR ROSMAIDAR, HASRIATI HASRIATI, NONI ZAKIAH
Format: Article
Language:English
Published: Universitas Syiah Kuala, Faculty of Mathematics and Natural Science 2024-11-01
Series:Jurnal Natural
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Online Access:https://jurnal.usk.ac.id/natural/article/view/33237
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author DANIEL DANIEL
FRENGKI FRENGKI
MUHAMMAD JALALUDDIN
WAHYU EKA SARI
ROSMAIDAR ROSMAIDAR
HASRIATI HASRIATI
NONI ZAKIAH
author_facet DANIEL DANIEL
FRENGKI FRENGKI
MUHAMMAD JALALUDDIN
WAHYU EKA SARI
ROSMAIDAR ROSMAIDAR
HASRIATI HASRIATI
NONI ZAKIAH
author_sort DANIEL DANIEL
collection DOAJ
description Doxorubicin chemotherapy has been a strong focus in breast cancer research. Side effects, toxicity and resistance have been extensively studied. One proposed solution to these issues that its combination with deoxyelephantopin. Deoxyelephantopin is known to be toxic in many cancer cells but safe in normal cells. IC50 of each compound were determined by using a MTT assay, and the MDR-1 gene mRNA expression were determined by using qPCR method, while the interaction of doxorubicin in combination with deoxyelephantonin on Pgp receptor were predicted by using an in silico approach. The IC50 of deoxyelephantopin was found to be 11.2 µg/mL, while IC50 of doxorubicin was 448 nM IC50 values showed a deoxyelephantopin-doxorubicin combination was able to reduce MDR-1 expression by 19% compared to doxorubicin and ½ IC50 values indicated that the combination formula reduced the expression by 15% over doxorubicin alone. The affinity of doxorubicin and deoxyelephantopin is -12.16 kcal/mol and -9.51 kcal/mol, respectively, while the affinity of doxorubicin after combine with deoxyelephantopin decreases from -12,16 kcal/mol to -11,25 kcal/mol due to the release of one Leu 221 hydrogen bond. The combination of doxorubicin with deoxyelephantopin is able to reduce expression and suppress the function of the Pgp protein.
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publishDate 2024-11-01
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spelling doaj-art-551f44c237a647f7a9040d751cd7f0092025-08-20T03:13:54ZengUniversitas Syiah Kuala, Faculty of Mathematics and Natural ScienceJurnal Natural1411-85132541-40622024-11-0124314014510.24815/jn.v24i3.3323718988Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silicoDANIEL DANIEL0FRENGKI FRENGKI1MUHAMMAD JALALUDDIN2WAHYU EKA SARI3ROSMAIDAR ROSMAIDAR4HASRIATI HASRIATI5NONI ZAKIAH6Universitas Syiah KualaFaculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, IndonesiaFaculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, IndonesiaFaculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, IndonesiaFaculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, IndonesiaFaculty of Medicine, University of Andalas, Padang, IndonesiaDepartment of Pharmacy, Health Polytechnic, Ministry of Health, Aceh, IndonesiaDoxorubicin chemotherapy has been a strong focus in breast cancer research. Side effects, toxicity and resistance have been extensively studied. One proposed solution to these issues that its combination with deoxyelephantopin. Deoxyelephantopin is known to be toxic in many cancer cells but safe in normal cells. IC50 of each compound were determined by using a MTT assay, and the MDR-1 gene mRNA expression were determined by using qPCR method, while the interaction of doxorubicin in combination with deoxyelephantonin on Pgp receptor were predicted by using an in silico approach. The IC50 of deoxyelephantopin was found to be 11.2 µg/mL, while IC50 of doxorubicin was 448 nM IC50 values showed a deoxyelephantopin-doxorubicin combination was able to reduce MDR-1 expression by 19% compared to doxorubicin and ½ IC50 values indicated that the combination formula reduced the expression by 15% over doxorubicin alone. The affinity of doxorubicin and deoxyelephantopin is -12.16 kcal/mol and -9.51 kcal/mol, respectively, while the affinity of doxorubicin after combine with deoxyelephantopin decreases from -12,16 kcal/mol to -11,25 kcal/mol due to the release of one Leu 221 hydrogen bond. The combination of doxorubicin with deoxyelephantopin is able to reduce expression and suppress the function of the Pgp protein.https://jurnal.usk.ac.id/natural/article/view/33237deoxyelephantopin, doxorubicin, mcf-7 cell line, pgp resceptors
spellingShingle DANIEL DANIEL
FRENGKI FRENGKI
MUHAMMAD JALALUDDIN
WAHYU EKA SARI
ROSMAIDAR ROSMAIDAR
HASRIATI HASRIATI
NONI ZAKIAH
Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico
Jurnal Natural
deoxyelephantopin, doxorubicin, mcf-7 cell line, pgp resceptors
title Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico
title_full Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico
title_fullStr Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico
title_full_unstemmed Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico
title_short Multi-drug resistance-1 (MDR-1) gene expression in MCF-7 cells after treated with doxorubicin-deoxyelephantopin combination and prediction of inhibitory activity against Pgp receptors with in silico
title_sort multi drug resistance 1 mdr 1 gene expression in mcf 7 cells after treated with doxorubicin deoxyelephantopin combination and prediction of inhibitory activity against pgp receptors with in silico
topic deoxyelephantopin, doxorubicin, mcf-7 cell line, pgp resceptors
url https://jurnal.usk.ac.id/natural/article/view/33237
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