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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...

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Autores principales: Botlagunta, Mahendran, Kollapalli, Bhulakshmi, Kakarla, Lavanya, Gajarla, Siva Priya, Gade, Sai Pujitha, Dadi, Chandra Lekha, Penumadu, Akhila, Javeed, Shaik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2016
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).
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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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