In silico study of curcumol, curcumenol, isocurcumenol, and Î²-sitosterol as potential inhibitors of estrogen receptor alpha of breast cancer
Background: Based on data from the Hospital Information System (HIS) in 2007, breast cancer is the top ranked diagnosed cancer in Indonesia. Estrogen receptor alpha (ERÎ±) is associated with breast cancer because it is found in high levels in cancer tissues. Curcumol, curcumenol, isocurcumenol of white tumeric rhizomes (Curcuma zedoaria (Christm.) Roscoe), and Î²-sitosterol from seeds of pumpkin (Cucurbita pepo L.) have been reported to have inhibitory activity against cancer cells. This study presents the in silico study of these compounds as inhibitors of ERÎ±.
Methods: Docking simulations are carried out in this paper to visualize molecular-level interactions between the four compounds with ERÎ±. Docking simulations between estradiol and tamoxifen on ERÎ± are carried out as well.
Results: Docking results indicated that curcumol, curcumenol, isocurcumenol, and Î²-sitosterol showed inhibitory activity againts estrogen receptor alpha (ERÎ±).Â The order of potency is shown consecutively by isocurcumenol, curcumol, curcumenol, and Î²-sitosterol with values 0.584 M, 1.36 M, 1.61 M, and 7.35 M respectively. Curcumenol and estradiol interacts with ERÎ± through hydrogen bonds and hydrophobic interactions, whereas curcumol, isocurcumenol, Î²-sitosterol and tamoxifen through hydrophobic interactions in succession.
Conclusion: Natural products containing all four compounds have the potential to be used as drugs or adjuvant drugs in breast cancer therapy.
Keywords: Î²-sitosterol, breast cancer, curcumol, curcumenol, estradiol, ERÎ±, isocurcumenol
Departemen Kesehatan Republik Indonesia. Profil Kesehatan Indonesia 2008. Jakarta: Departemen Kesehatan Republik Indonesia. 2009; 66. Indonesian.
Ikeda K, Inoue S. Estrogen receptor and their downstream targets in cancer. Arc Histol Cytol. 2004;67(5):435-42. http://dx.doi.org/10.1679/aohc.67.435
Murphy AJ, Guyre PM, Wira CR, Pioli PA. Estradiol Regulates Expression of Estrogen Receptor ERÎ±46 in Human Macrophages. PLoS ONE. 2009;4(5):1-11. http://dx.doi.org/10.1371/journal.pone.0005539
Clemons M, Goss P. Estrogen and the Risk of Breast Cancer. N Engl J Med. 2001;344:276-85. http://dx.doi.org/10.1056/NEJM200101253440407
Lin CY, Strom A, Vega VB, Kong SL, Yeo AL, Thomsen JS, et al. Discovery of estrogen receptor a target genes and response elements in breast tumor cells. Genome Biol. 2004;5(9):R66. http://dx.doi.org/10.1186/gb-2004-5-9-r66
Tanenbaum D, Wang Y, Williams SP, Sigler PB. Crystallographic comparison of the estrogen and progesterone receptorâs ligand binding domains. Proc Natl Acad Sci USA. 1998;95(11):5998-6003. http://dx.doi.org/10.1073/pnas.95.11.5998
Khine M M. Isolation and characterization of phytoconstituents from Myanmar medicinal plants. [disertation]. Wittenberg: Der Martin Luther UniversitÃ¤t Halle; 2006.
N, Triaspolitica. "Kanker Payudara: Informasi, Penyebab, Gejala, Stadium Dan Pengobatan." Mau Nanya Dong Dok. N.p, 28 June 2017. Web. 30 June 2017.Retreived from: https://nanyadongdok.blogspot.com/2017/06/kanker-payudara-informasi-penyebab.html.
Xu LC, Bian KJ, Liu ZM, Zhou J, Wang G. The inhibitory effect of curcumol on women cancer cells and synthesis of RNA. Tumor. 2005;25(6):570-2.
Han XH, Ye YY, Guo BF, Liu S. Effects of platycodin D in combination with different active ingredients of Chinese herbs on proliferation and invasion of 4T1 and MDA-MB-231 breast cancer cell lines. Zhong Xi Yi Jie He Xue Bao. 2012;10(1):67-75. Chinese. http://dx.doi.org/10.3736/jcim20120111
Chevallier A. The Encyclopedia of Medicinal Plants. London: Wolfe Publishing Ltd; 1996.
Ardabili AG, Farhoosh G, Khodaparast MHH. Chemical composition and physicochemical properties of pumpkin seeds (Cucurbita pepo Subsp. Pepo Var. Styriaka) Grown in Iran. J Agr Sci Tech. 2011;13:1053-63.
Matsuoka K, Nakazawa T, Nakamura A, Honda C, Endo K, Tsukada M. Study of thermodynamic parameters for solubilization of plant sterol and stanol in bile salt micelles Chem Phys Lipids. 2008;154(2):87-93. http://dx.doi.org/10.1016/j.chemphyslip.2008.05.002
Awad AB, Barta SL, Fink CS, Bradford PG. Î²-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism. Mol Nutr Food Res. 2008;52(4):419-26. http://dx.doi.org/10.1002/mnfr.200700222
Chai JW, Kuppusamy UR, Kanthimathi MS. Beta-sitosterol Induces Apoptosis in MCF-7 Cells. Malaysian Journal of Biochemistry and Molecular Biology 2008;16(2):28-30.
Lipinski CA, Lombardo F, Dominy BW and Feeney PJ. 2001. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3-26. http://dx.doi.org/10.1016/S0169-409X(00)00129-0
Kontoyianni M, McClellan LM, Sokol GS. Progress in Medicinal Chemistry. J. Med. Chem. 2004;36:63-4.
Jones G, Willet P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol. 1997;267(3):727-48. http://dx.doi.org/10.1006/jmbi.1996.0897
Bohm HJ, Schneider G. Protein-ligand interactions from molecular recognition to drug design. Weinheim: Wiley-VCH. 2003.p.38-9. http://dx.doi.org/10.1002/3527601813
Mustarichie R, Saptarini NM, Levita J. The Study of the interaction of quercetin and casticin with H4r, anti-inflammatory receptor, as supporting data for anti-inflammatory herbal medicine. Journal of Computer Science, Technology and Application. 2012;1(1):70-76.
Mantovani A, Allavena P, Sica A and Balkwill F. Cancer-related inflammation Nature. 2008;454:436-44. http://dx.doi.org/10.1038/nature07205
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