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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 Sub; Bak, Yesol; Park, Yun Sun; Lee, Dong Hun; Kim, Jung Hee; Kang, Jeong Woo; Song, Hyuk-Hwan; Oh, Sei-Ryang; Yoon, Do Young
- Issue Date
- Cell Biology and Toxicology, 29(4), 259-272
- Article Type
- Anti-Tumor; Apoptosis; Cancer Cell; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Strain; Cell Strain C33A; Cell Strain CaSki; Cell Strain SiHa; Cervical Cancer; Controlled Study; Down-Regulation; Drug Cytotoxicity; Drugs, Chinese Herbal; Female; Flavanones; Flavonoid; Flavonoids; Genetic Transfection; Human; Human Cell; Human Papillomavirus; Human Papillomavirus 16; Human Papillomavirus Type 16; Humans; Membrane Potential, Mitochondrial; Mitochondrial Membrane Potential; Nicotinamide Adenine Dinucleotide Adenosine Diphosphate Ribosyltransferase; Oncogene; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Papillomavirus Infection; Papillomavirus Infections; Plant Extracts; Priority Journal; Protein Bax; Protein BCL 2; Protein Cleavage; Protein E6; Protein E7; Protein Expression; Protein Processing; Protein Targeting; Repressor Proteins; RNA Interference; RNA, Small Interfering; Scutellaria Baicalensis; Signal Transduction; Small Interfering Rna; Uterine Cervical Neoplasms; Uterine Cervix Cancer; Virus Cell Interaction; Virus DNA; Virus Gene; Wogonin
- 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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