title: Evaluation and Elucidation Studies of Natural Aglycones for Anticancer Potential using Apoptosis-Related Markers: An In silico Study.
abstract: Exposure to exogenous and endogenous chemicals and subsequent cellular and molecular changes has been linked to enhanced cell proliferation and restricted apoptosis phenomenon. Though in the past decades numerous anticancer drugs inducing programmed cell death in cancer cells by targeting specific apoptotic markers have reached the market, they have been allied with unwanted side effects, ranging from mild to severe toxicity. With further understanding on the functional mechanism of p53 and MDM2 in apoptosis and in our continuous search for new and potent multi-target anticancer lead compounds, we have carried out molecular docking and inhibition studies of the selected aglycones along with selected anticancer leads, against the specific apoptotic and cell cycle markers using AutoDock Tools 4.0 and other computational softwares. The docking results have been analyzed in terms of binding energies (kcal/mol) and inhibition constant (µM). The study clearly proposes our aglycones [solanidine (Solanid-5-en-3β-ol), solasodine (Solasod-5-en-3β-ol), and tomatidine (5α-Tomatidan-3β-ol)] induce apoptosis by inhibiting the p53-MDM2 complex, p21Waf1/Cip1, and Bcl-2 proteins, which were even found comparable with the anticancer drugs nutlin and/or halofuginone. The work further emphasizes that the individual molecular targets such as BAX and Bcl-2 may result in misleading data at any level; however, ratio of responses to BAX and Bcl-2 shall be considered for better clue about a compound to be pro- or anti-apoptotic.
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, 226026, India.|Advanced Centre for Bioengineering and Bioinformatics (ACBB), Integral Research Centre (IRC), Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Uttar Pradesh, 226026, India.
authors.forename: Salman
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, 226026, India.|Advanced Centre for Bioengineering and Bioinformatics (ACBB), Integral Research Centre (IRC), Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Uttar Pradesh, 226026, India.
authors.forename: M Kalim A
authors.initials: MKA
authors.lastname: Khan
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, 226026, India. jmarif@gmail.com.|Department of Biochemistry, College of Medicine, University of Hail, P.O. Box 2440, Hail, Kingdom of Saudi Arabia. jmarif@gmail.com.
authors.forename: Jamal M
authors.initials: JM
authors.lastname: Arif
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D012015:Reference Standards; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D007211:Indoles
keywords: Apoptosis; BAX; BAX/Bcl-2 ratio; Molecular docking; p53–MDM2 complex