Title

In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3

Authors

Mahendran Botlagunta1,2*, Bhulakshmi Kollapalli1, Lavanya Kakarla1, Siva Priya Gajarla1, Sai Pujitha Gade1, Chandra Lekha Dadi1, Akhila Penumadu1 and Shaik Javeed1

Affiliation

1Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India; 2Sweety Biologicals India Private Limited, Kavali, Andhra Pradesh-524201, India.

Email

Dr. Mahendran Botlagunta- E-mail: bmnchowdary@gmail.com; *Corresponding author

Article Type

Hypothesis

Date

Received June 14, 2016; Revised September 9, 2016; Accepted October 12, 2016; Published October 18, 2016

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).

Keywords:

In vitro, anti-cancer activity, doxorubicin, human RNA helicase, DDX3

Citation

Botlagunta et al. Bioinformation 12(7): 347-353 (2016)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

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.