Volume: 3, Issue: 6, June, 2013
Cytotoxicity Studies of Xanthorrhizol and Its Mechanism Using Molecular Docking Simulation and Pharmacophore ModellingAuthor Affiliations
Xanthorrhizol (XNT) is one of major compounds from temulawak`s rhizome and its activity in several cancer cells is known. The aim of this study was to identify mechanism of xanthorrhizol from temulawak`s rhizome as an hERα inhibitor against breast cancer human cell lines. The cytotoxicity of XNT from temulawak`s rhizome on T47D human breast cancer cells lined by sulforhodamine B (SRB) method has been carried out, while molecular docking simulation and pharmacophore modelling methods were employed to predict mechanism of xanthorrhizol as hER inhibitor. Cytotoxicity studies showed that XNT of the isolated and standard had an IC50 100 and 55.50 µg/mL in T47D cells, respectively. Subsequently, molecular docking interaction showed that XNT might be able to compete with estradiol (E2) as a potential ERα inhibitor with the calculated binding free-energy of -8.2 kcal/mol, even the compound superimposed with tamoxifen (4-OHT). XNT formed hydrogen bonds with Arg394 and Glu353 as mention E2 and tamoxifen also formed same interaction with same residue and interacted hydrophobic bonds similar to 4-OHT with: Leu387, Leu384, Leu391, Phe404, L349, Leu346, Met388, and Leu525 of estrogen alpha Ligan Binding Domain (LBD), although 4-OHT indicated stronger hydrophobic when the tail of tamoxifen interacted with Tyr347, Asp351, Trp383 and Leu428. XNT missed two chemical features into HipHop models pharmacophore thus may result in reduced inhibitory activity against T47D compared than 4-OHT. The xanthorrhizol mechanism as a hER inhibitor is postulated as partial estrogen antagonist, is justifiable based on its competitive characteristic versus tamoxifen (OHT-200) which was located on the active side of HER-α.
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