Lysine specific demethylase 1 as therapeutic target of cancer

Nihar Ranjan Panda, Sudhir Ranjan Bhoi, Rakesh M. Rawal, Mukesh Kumar Raval

Abstract


Objective: Lysin specific demethylase 1 (LSD1) inhibits the tumor suppressor activity of p53 and facilitates the progress of tumor. In order to check the tumor growth, the activity of LSD1 enzyme is to be blunted.

Methods: Phytochemicals from naturally occurring plant-based anti-cancer compound-activity-target (NPACT) database are screened with LSD1 as target applying genetic algorithm (GA) method to study best ligand poses and free energy of binding using Argus Lab. The prediction of drug-likeness and oral toxicity of the ligands are performed by the online tools Molsoft and ProTox respectively.

Results: Calyxin H shows optimum binding affinity to both the substrate and FAD binding sites of LSD1. The LD50 value (median lethal dose) of calyxin H is more than 1000 mg/kg body weight and the toxicity class is 4.

Conclusions: Calyxin H is the inhibitor of choice against target LSD1. The lead molecule may be the future potential herbal drug for cancer treatment.


Keywords


Anti-cancer, LSD1, Calyxin H, Phytochemical, Drug-likeness, Toxicity

Full Text:

PDF HTML XML

References


Chen Y, Jie W, Yan W, Zhou K, Xiao Y. Lysine-specific histone demethylase 1 (LSD1): A potential molecular target for tumor therapy. Critical reviews in eukaryotic gene expression 2012;22:53-9.

Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, et al. p53 is regulated by the lysine demethylase LSD1 Nature 2007;449:105-8.

Kosumi K, Baba Y, Sakamoto A, Ishimoto T, Harada K, Nakamura K, et al. Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer. Int J Cancer. 2016;138:428-39.

Sak K. Chemotherapy and dietary phytochemical agents. Chemotherapy Res Practice. 2012;282570:11.

Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr. EE, Brice MD, Rodgers JR, et al. The Protein Data Bank: A computer-based archival file for macromolecular structures. J Mol Biol. 1977;112:535.

Mangal M, Sagar P, Singh H, Raghava GPS, Agarwal SM. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database Nucleic Acids. Res. 2013;41:D1124–9.

Mark AT. ArgusLab 4.0, Planaria Software LLC, Seattle, Avaliable at: http://www.ArgusLab.com Accessed on 3 March 2017.

Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. ProTox: a web server for the in silico prediction of rodent oral toxicity Nucleic Acids. Res (Web server issue 2014).

Ahmed J, Worth CL, Thaben P, Matzig C, Blasse C, Dunkel M, et al. Fragment Store a comprehensive database of fragments linking metabolites, toxic molecules and drugs. Nucleic Acids Res. 2011;39:D960–7.

Froimowitz M. HyperChem. a software package for computational chemistry and molecular modelling. Biotechniques. 1993;14:1010-3.

Wang J, Lu1 F, Ren Q, Sun H, Xu Z, Lan R, et al. Novel histone demethylase LSD1 Inhibitors selectively target cancer cells with psuripotent stem cell Properties. Cancer Res. 2011;71:7238–49.

Ali MS, Banskota AH, Tezuka Y, Saiki I, Kadota S. Antiproliferative activity of diarylheptanoids from the seeds of Alpinia blepharocalyx. Biol Pharm Bull. 2001;24(5):525-8.






Copyright (c) 2017 Pharmaceutical and Biological Evaluations

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.



Creative Commons License

 

© Copyright 2017 - Pharmaceutical and Biological Evaluations