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Eur J Pharmacol. 2014 Dec 5;744:132-46. doi: 10.1016/j.ejphar.2014.09.048. Epub 2014 Oct 18.

Berberine alters epigenetic modifications, disrupts microtubulenetwork, and modulates HPV-18 E6-E7 oncoproteins by targeting p53in cervical cancer cell HeLa: a mechanistic study including moleculardocking.Saha SK , Khuda-Bukhsh AR .

AbstractIncreased evidence of chemo-resistance, toxicity and carcinogenicity necessitates search foralternative approaches for determining next generation cancer therapeutics and targets. Wetherefore tested the efficacy of plant alkaloid berberine on human papilloma virus (HPV) -18positive cervical cancer cell HeLa systematically-involving certain cellular, viral and epigeneticfactors. We observed disruptions of microtubule network and changes in membrane topologydue to berberine influx through confocal and atomic force microscopies (AFM). We examinednuclear uptake, internucleosomal DNA damages, mitochondrial membrane potential (MMP)alterations and cell migration assays to validate possible mode of cell death events. Analyticaldata on interactions of berberine with pBR322 through fourier transform infrared (FTIR) andgel migration assay strengthen berberine׳s biologically significant DNA binding abilities. Wemeasured cellular uptake, DNA ploidy and DNA strand-breaks through fluorescence activatedcell sorting (FACS). To elucidate epigenetic modifications, in support of DNA bindingassociated processes, if any, we conducted methylation-specific restriction enzyme (RE)assay, methylation specific-PCR (MSP) and expression studies of histone proteins. We alsoanalyzed differential interactions and localization of cellular tumor suppressor p53 and viraloncoproteins HPV-18 E6-E7 through siRNA approach. We further made in-silico approachesto determine possible binding sites of berberine on histone proteins. Overall results indicatedcellular uptake of berberine through cell membrane depolarization causing disruption ofmicrotubule networks and its biological DNA binding abilities that probably contributed toepigenetic modifications. Results of modulation in p53 and viral oncoproteins HPV-18 E6-E7by berberine further proved its potential as a promising chemotherapeutic agent in cervicalcancer.

Copyright © 2014 Elsevier B.V. All rights reserved.

Berberine; Berberine (Pubchem SID_162173365); Cell signaling; Cervical cancer;Cytoskeleton structures; Epigenetic modification; Molecular docking

PMID: 25448308 [PubMed - indexed for MEDLINE]

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Berberine alters epigenetic modifications, disrupts microtubul... http://www.ncbi.nlm.nih.gov/pubmed/25448308

2 of 2 30/04/16 17:19