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In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3
RNA helicase, DDX3 is a multifunctional enzyme and is known to be associated with several diseases like HIV progression, brain and breast cancer. Some of the ring expanded nucleoside compounds such as REN: NZ51, fused di imidazodiazepine ring (RK33), (Z)-3-(5- (3-bromo benzylidene)-4-oxo-2-thioxothi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Biomedical Informatics
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311078/ https://www.ncbi.nlm.nih.gov/pubmed/28246464 http://dx.doi.org/10.6026/97320630012347 |
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author | Botlagunta, Mahendran Kollapalli, Bhulakshmi Kakarla, Lavanya Gajarla, Siva Priya Gade, Sai Pujitha Dadi, Chandra Lekha Penumadu, Akhila Javeed, Shaik |
author_facet | Botlagunta, Mahendran Kollapalli, Bhulakshmi Kakarla, Lavanya Gajarla, Siva Priya Gade, Sai Pujitha Dadi, Chandra Lekha Penumadu, Akhila Javeed, Shaik |
author_sort | Botlagunta, Mahendran |
collection | PubMed |
description | RNA helicase, DDX3 is a multifunctional enzyme and is known to be associated with several diseases like HIV progression, brain and breast cancer. Some of the ring expanded nucleoside compounds such as REN: NZ51, fused di imidazodiazepine ring (RK33), (Z)-3-(5- (3-bromo benzylidene)-4-oxo-2-thioxothiazolidin-3-yl)-N-(2- hydroxy phenyl) propanamide compound (FE15) have been documented to inhibit DDX3 helicase activity. However, synthesis of these drugs is limited to few research groups. Prevalence of literature study, we found that doxorubicin form strong hydrogen bond interactions with crystallized form of DDX3 using in-silico molecular docking approach. To evaluate the biological inhibitory action of doxorubicin, we performed the ATPase activity assay and anti-cancer activity using H357 cancer cell lines. Results showed that doxorubicin continually declined the inorganic phosphate (Pi) release and inhibited the ATP hydrolysis by directly interacting with DDX3. Anticancer activity was detected by MTT assay. The half maximal inhibitory concentrations of doxorubicin (IC50) for H357 cancer cell line is 50 μM and also doxorubicin significantly down regulated the expression of DDX3. Taken together, our results demonstrate, that inhibition of DDX3 expression by using doxorubicin can be used as an ideal drug candidate to treat DDX3 associated cancer disorder by interacting with unique amino acid residues (Thr 198) and common amino acid residues (Tyr 200 and Thr 201). |
format | Online Article Text |
id | pubmed-5311078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Biomedical Informatics |
record_format | MEDLINE/PubMed |
spelling | pubmed-53110782017-02-28 In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 Botlagunta, Mahendran Kollapalli, Bhulakshmi Kakarla, Lavanya Gajarla, Siva Priya Gade, Sai Pujitha Dadi, Chandra Lekha Penumadu, Akhila Javeed, Shaik Bioinformation Hypothesis RNA helicase, DDX3 is a multifunctional enzyme and is known to be associated with several diseases like HIV progression, brain and breast cancer. Some of the ring expanded nucleoside compounds such as REN: NZ51, fused di imidazodiazepine ring (RK33), (Z)-3-(5- (3-bromo benzylidene)-4-oxo-2-thioxothiazolidin-3-yl)-N-(2- hydroxy phenyl) propanamide compound (FE15) have been documented to inhibit DDX3 helicase activity. However, synthesis of these drugs is limited to few research groups. Prevalence of literature study, we found that doxorubicin form strong hydrogen bond interactions with crystallized form of DDX3 using in-silico molecular docking approach. To evaluate the biological inhibitory action of doxorubicin, we performed the ATPase activity assay and anti-cancer activity using H357 cancer cell lines. Results showed that doxorubicin continually declined the inorganic phosphate (Pi) release and inhibited the ATP hydrolysis by directly interacting with DDX3. Anticancer activity was detected by MTT assay. The half maximal inhibitory concentrations of doxorubicin (IC50) for H357 cancer cell line is 50 μM and also doxorubicin significantly down regulated the expression of DDX3. Taken together, our results demonstrate, that inhibition of DDX3 expression by using doxorubicin can be used as an ideal drug candidate to treat DDX3 associated cancer disorder by interacting with unique amino acid residues (Thr 198) and common amino acid residues (Tyr 200 and Thr 201). Biomedical Informatics 2016-10-18 /pmc/articles/PMC5311078/ /pubmed/28246464 http://dx.doi.org/10.6026/97320630012347 Text en © 2016 Biomedical Informatics http://creativecommons.org/licenses/by/3.0/ This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |
spellingShingle | Hypothesis Botlagunta, Mahendran Kollapalli, Bhulakshmi Kakarla, Lavanya Gajarla, Siva Priya Gade, Sai Pujitha Dadi, Chandra Lekha Penumadu, Akhila Javeed, Shaik In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 |
title | In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 |
title_full | In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 |
title_fullStr | In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 |
title_full_unstemmed | In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 |
title_short | In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3 |
title_sort | in vitro anti-cancer activity of doxorubicin against human rna helicase, ddx3 |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311078/ https://www.ncbi.nlm.nih.gov/pubmed/28246464 http://dx.doi.org/10.6026/97320630012347 |
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