In Silico Studies of Bioactive Compounds from Hibiscus rosa-sinensis Against HER2 and ESR1 for Breast Cancer Treatment
DOI:
https://doi.org/10.37285/ijpsn.2021.14.6.3Abstract
The most common type of cancer and the second biggest cause of death is breast cancer. The disease is the leading cause of death in women aged 45 to 55. It's a multi-stage disease in which viruses have a role in one stage. Breast cancer is an illness that affects the sufferer, their family, and the entire community all over the world. Breast cancer has no established cause, however specific risk factors have been found. Age, race, gender, and family history are all fixed and immutable characteristics. Other elements, such as social and familial support, can help to mitigate the harmful effects.The aim of the present study was to investigate the bioactive ligand for the breast cancer treatment against the HER2 and ESR1 proteins by molecular docking studies. HER2 is an oncogene and membrane tyrosine kinase that is overexpressed and gene amplified in about 20% of breast tumours. When active, it sends proliferative and anti-apoptotic signals to the cell. It is the most important factor in the genesis and progression of breast cancer tumours. To carry out this work protein structures were download from the PDB database and ligands three dimensional structures were downloaded from the PubChem database. The docking was performed by using the iGEMDOCK software suit. The binding energies of bioactive molecules from Hibiscus rosa-sinensis were found to be Rutin (-139.779, -102.743), Quercetin (-106.5, -99.7807), Kaempferol (-105.824, -92.5271), Myricetin (-111.913, -99.603) and Methotrexate (-140.69, -130.165) against HER2 and ESR1 proteins respectively. Lowest energy of Rutin compared to Methotrexate showed highest binding among the other bioactive molecules.The binding energies of the molecules are the sum of hydrogen bond, vanderwaal’s and electrostatic energies that inversely linked to protein-ligand interaction. From the result of the current study we can conclude that among the four bioactive molecule rutin has lowest binding energy so it could be used as an inhibitor of HER2 and ESR1 protein for the treatment of breast carcinoma in future.
Downloads
Metrics
Keywords:
in-silico, iGEMDOCK, Breast cancer, HER2, ESR1, Rutin
Downloads
Published
How to Cite
Issue
Section
References
Agrawal KK (2020). A Review on Pharmacological Validation of genus Hibiscus with main Emphasis on Hibiscus rosa-sinensis.Int J Pharm Pharm Res 18(3): 451-462.
Agrawal KK, Gupta JK, Verma A and Singh K (2012). Preliminary phytochemical and in-vitro anthelmintic screening of Hibiscus rosa-sinensis Linn. Flower Extracts, Novel Science Int J Pharm Sci 1(7): 446-448.
Agrawal KK, Mishra UK, Singh K and Mishra P (2015). Comparative anthelmintic activity of ethanolic extracts of Hibiscus rosa sinensisLinn. flower with Aegle marmelos leaves. Der Pharmacia Lettre 7(10): 185-187.
Agrawal KK and Singh K (2017). Hair Growth Activity of Aqueous Extract of Hibiscus Rosa-sinensis L. Flowers. Indian J Drugs 5(4): 142-149.
Agrawal KK, Verma A and Singh K (2019). Gastro-protective potential of flowers of Hibiscus rosa-sinensis (L) in mucosal lesion on rats. Indian Drugs 56: 25-31.
Batra P and Sharma AK (2013). Anti-cancer potential of flavonoids: Recent trends and future perspectives. Biotech 3: 439–459.
Calder M and Burgos E(2011). A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 11: 298–344.
Chen AY and Chen YC (2013). A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem138: 2099–2107.
Creighton CJ (2012). The molecular profile of luminal B breast cancer. Biol Targets Ther 6: 289–297.
Devi KP, Rajavel T, Habtemariam S, Nabavi SF, Nabavi SM (2015). Molecular mechanisms underlying anticancer effects of myricetin. Life Sci 142: 19–25.
Dixon RA (2001). Natural products and plant disease resistance. Nature 411: 843–847.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al., (2013). Cancer incidence and mortality worldwide. IARC11.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893–2917.
Granado-Serrano AB, Martin MA, Bravo L, Goya L and Ramos S (2010). Quercetin modulates nf-kappa b and ap-1/jnk pathways to induce cell death in human hepatoma cells. Nutr Cancer 62: 390–401.
Hanahan D and Weinberg RA (2011). Review hallmarks of cancer: The next generation. Cell 144: 646–674.
Hanahan. D, Weinberg RA and Francisco S (2000). The hallmarks of cancer review university of california at sanfrancisco. Cell 100: 57–70.
Hsu KC, Chen YF, Lin SR and Yang JM (2011). iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis, BMC Bioinformatics 12(Suppl1): S33
Hedenfalk I (2006). Gene expression profiling can distinguish tumor subclasses of breast carcinomas. In Gene Expression Profiling by Microarrays: Clinical Implications; Cambridge University Press: Cambridge, UK, pp. 289–297.
Igney FH and Krammer PH(2002). Death and anti-death: Tumour resistance to apoptosis. Nat Rev 2: 277–288.
Iqbal J, Abbasi BA, Mahmood T, Kanwal S, AliB and Shah SA (2017). Plant-derived anticancer agents: A green anticancer approach. Asian Pac J Trop Biomed 7: 1129–1150.
Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ (2009). Cancer statistics.Cancer J Clin 59: 225-49.
King CR, Krausmh and Aaronsons A (1985). Amplification of a novel verbB-related gene in human mammary carcinoma. Science 229: 974–976.
Kumar NA, Sharmila R, Akila K and Jaikumar B (2016). In-Silico Approach for the Assessment of Oral Cancer Property on Limoniaacidissima. Int J Pharm Sci Res 7(3): 1271-75.
Kelly GS (2011). Quercetin. Altern Med Rev 16: 172–194.
Knickle A, Fernando W, Greenshields AL, Rupasinghe HPV and Hoskin DW (2018). Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide. Food Chem Toxicol 118: 154–167.
Kushner PJ and Agard DA (2000). Estrogen receptor pathways to AP-1. J Steroid Biochem Mol Biol 74: 11–17.
Levitsky DO and Dembitsky VM (2015). Anti-breast Cancer Agents Derived from Plants. Nat Prod Bioprospect 5:1–16.
Liu RH (2004). Nutrition, and cancer potential synergy of phytochemicals in cancer prevention: Mechanism of action 1. Int Res Conf Food Nutr Cancer Potential 134: 3479–3485.
Li MJ (2014). Green tea compounds in breast cancer prevention and treatment. World J Clin Oncol 5: 520.
Luo H, Daddysman MK, Rankin GO, Jiang BH and Chen YC (2010). Kaempferol enhances cisplatin’s effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cmyc. Cancer Cell Int 10: 1–9.
Normanno N, Bianco C and Strizzi L (2005). The ErbB receptors and their ligands in cancer: an overview. Curr Drug Targets 6(3): 243–257.
Natalija DP, Ana K and Damir V (2012). Role of HER2 signaling pathway in breast cancer: biology, detection and therapeutical implications.Period Biol 114(4): 505–510.
Osborne CK, Schi R (2011). Mechanisms of Endocrine Resistance in Breast Cancer. Annu Rev Med 62: 233–247.
Prakash O, Kumar A and Kumar P(2013). Anticancer potential of plants and natural products: A review. Am J Pharmacol Sci 1: 104–115.
Panche AD, Diwan AD and Chandra SR (2016). Flavonoids: An overview. J Nutr Sci 5: 1–15.
Roskoski Jr R (2014). The ErbB/HER family of protein-tyrosine kinases and cancer, Pharmacol Res 79: 34-74.
Renoir JM, Marsaud V and Lazennec G (2013). Estrogenrece ptorsignaling as a target for novel breast cancer therapeutics. Biochem Pharmacol 85(4):449-465.
Ravishankar D, Rajora AK, Greco F and Osborn HMI (2013). Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol 45: 2821–2831.
Safarzadeh E, Shotorbani SS and Baradaran B (2014). Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull 4: 421–427.
Sergina NV and Moasser MM (2007). The HER family and cancer: emerging molecular mechanisms and therapeutic targets. Trends Mol Med 13(12): 527-534.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullricha and Mcguirewl (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 235: 177–182.
Tapas AR, Sakarkar DM and Kakde RB (2008). Flavonoids as nutraceuticals: A review. Trop J Pharm Res 7:1089–1099.
Varghese E, Samuel SM, Abotaleb M. Cheema S, Mamtani R and Busselberg, D (2018). The “yin and yang” of natural compounds in anticancer therapy of triple-negative breast cancers. Cancers 10: 346.
Yang JM and Chen CC (2004). GEMDOCK: a generic evolutionary method for molecular docking. Proteins 55: 288-304.
