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Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells

Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells
Kim, Man SubBak, YesolPark, Yun SunLee, Dong HunKim, Jung HeeKang, Jeong WooSong, Hyuk-HwanOh, Sei-RyangYoon, Do Young
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Anti-TumorApoptosisCancer CellCaspase 3Caspase 9Cell Line, TumorCell StrainCell Strain C33ACell Strain CaSkiCell Strain SiHaCervical CancerControlled StudyDown-RegulationDrug CytotoxicityDrugs, Chinese HerbalFemaleFlavanonesFlavonoidFlavonoidsGenetic TransfectionHumanHuman CellHuman PapillomavirusHuman Papillomavirus 16Human Papillomavirus Type 16HumansMembrane Potential, MitochondrialMitochondrial Membrane PotentialNicotinamide Adenine Dinucleotide Adenosine Diphosphate RibosyltransferaseOncogeneOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionPapillomavirus InfectionsPlant ExtractsPriority JournalProtein BaxProtein BCL 2Protein CleavageProtein E6Protein E7Protein ExpressionProtein ProcessingProtein TargetingRepressor ProteinsRNA InterferenceRNA, Small InterferingScutellaria BaicalensisSignal TransductionSmall Interfering RnaUterine Cervical NeoplasmsUterine Cervix CancerVirus Cell InteractionVirus DNAVirus GeneWogonin
Wogonin is a flavonoid compound extracted from Scutellaria baicalensis and is well known as a benzodiazepine receptor ligand with anxiolytic effects. Many recent studies have demonstrated that wogonin modulates angiogenesis, proliferation, invasion, and tumor progress in various cancer tissues. We further explored the mechanism of action of wogonin on cervical cancer cells that contain or lack human papillomavirus (HPV) DNA. Wogonin was cytotoxic to HPV 16 (+) cervical cancer cells, SiHa and CaSki, but not to HPV-negative cells. We demonstrated that wogonin induced apoptosis by suppressing the expressions of the E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and SiHa cells. The modulation of p53 and protein retinoblastoma (pRb) were also triggered by the suppression of E6 and E7 expressions. However, p53 was not altered in HPV-negative cervical cancer C33A cells. Moreover, wogonin modulated the mitochondrial membrane potential and the expression of pro- and anti-apoptotic factors such as Bax and Bcl-2. Wogonin also provoked the cleavage of caspase-3, caspase-9, and poly ADP ribose polymerase. After transfection of siRNAs to target E6 and E7, additional restoration of p53 and pRb was not induced, but processing of caspases and PARP was increased compared with wogonin treatment alone. Together, our findings demonstrated that wogonin effectively promotes apoptosis by downregulating E6 and E7 expressions and promoting intrinsic apoptosis in human cervical cancer cells. © 2013 Springer Science+Business Media Dordrecht.
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