title: In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3.
abstract: 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).
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India; Sweety Biologicals India Private Limited,Kavali, Andhra Pradesh-524201, India.
authors.forename: Mahendran
authors.initials: M
authors.lastname: Botlagunta
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Bhulakshmi
authors.initials: B
authors.lastname: Kollapalli
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Kakarla
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Siva Priya
authors.initials: SP
authors.lastname: Gajarla
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Sai Pujitha
authors.initials: SP
authors.lastname: Gade
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Chandra Lekha
authors.initials: CL
authors.lastname: Dadi
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Akhila
authors.initials: A
authors.lastname: Penumadu
authors.affiliation: Department of Biotechnology, K L University, Guntur, Andhra Pradesh-522502, India.
authors.forename: Shaik
authors.initials: S
authors.lastname: Javeed
keywords: DDX3; RNA helicase; anti-cancer activity; doxorubicin