ABSTRACT
Background:Oral premalignancies are a group of disease or syndromes which if left untreatedcanleadtocancer.ItcarriesagreatsignificanceinIndianperspective. Theactual figure of oral cancers arising from oral premalignancies is not known and to predict accuratelythemalignanttransformationsofthemisstillnotpossible.Oxidativestressisa known player behind cancerogenesis. Recently decreased Paraoxonase-1 activity and increasedoxidativestressmarkerswarefoundtobeassociatedwithOralSquamousCell Carcinoma. So, thereis astrongpossibilityofasimilar findingin Oral Premalignanciestoo. Aim: This studyaims to investigatethecor-relation between serum PON-1 activityand oxidative stress markers (MDA& Vitamin C) in patients with Oral Premalignancies. MaterialandMethods:Atotalof62patientswithclinically diagnosedoralpremalignant lesions anddiseasedcontrolswerechosenforthe study. Venous bloodsampleswerecollectedandPON-1,MDA (inse-rum)&Vitaminc (inplasma) wereanalysed spectro-photometrically. Results:A significant decreased serum PON-1 activity (P<0.05) and concomitant significantlyincreased serum MDA(P<0.05)anddecreased Vitamin Clevels (P<0.05) were observedinpremalignanciescomparedtothecontrols.Thesefinding weremorepronounced inOral Leukoplakia (OL) thaninOral Submucous Fibrosis (OSMF)withasignificantdifference.Meanlevelsoftheanalysedparameters differedaccordinglyin theclinicalgrades of oral premalignancies. Conclusion:Itcanbeenvis-agedthatserumPON-1activity andincreasedoxidativestress mightbe acontributingfactorbehindpathogenesisandprogressionofOralPremalignant Diseases
ABSTRACT
Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.
Subject(s)
Female , Humans , Carrageenan , Computer Simulation , Curcumin , Drug Design , Hope , Human papillomavirus 16 , Mortality , Tumor Suppressor Protein p53ABSTRACT
Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB) domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.