Title

Inhibitory effect of flavonoids on mutant H-Rasp21 protein

Authors

Tariq A. Masoodi*, Adel H. Alhamdanz  

Affiliation

College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
 

Email

tahabioinfo@gmail.com; * Corresponding author

Article Type

Hypothesis

Date

Received March 20, 2010; accepted April 09, 2010; published June 15, 2010
 

Abstract

Mutant form of H-Ras (Harvey-Ras) proteins are found in almost 10%-25% of human tumours. Mutational activation transforms it into an oncogenic form, which results in the loss of intrinsic GTPase function and therefore the protein is constitutively in the active, GTP-bound state and is continuously sending signals for cell growth and proliferation. In the present insilico study, the inhibitory effect of different flavonoid compounds on mutant H Ras protein p21 has been assessed. In addition, inhibitory effect of flavonoids is compared with 3 known anticancer drugs. Upon docking, it was found that flavonoids such as Naringenin, Daidzein, and Hesperetin showed highest affinity (most negative ΔG), while Rutin showed no affinity towards mutant H Ras. The 3 clinical anticancer agents (Erlotinib, Letrozole and Exemestane) showed binding energies in the range of −1.11 to −5.51 kcal/mol which is comparatively lower than the flavonoids indicating efficacy of flavonoids in the treatment of cancer with little or no cytotoxicity. Our study demonstrates that flavonoids (particularly Naringenin, Daidzein, and Hesperetin) are the effective drugs to inhibit function of mutant H-Ras P21 protein, which in turn arrests the process of cell growth and proliferation of the cancer cell.

Keywords

Docking; flavonoids; cancer; H-Ras; Raf; autodock

Citation

Masoodi & Alhamdanz, Bioinformation 5 (1): 11-15 (2010)

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.