title: Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells.
abstract: 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.
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea.
authors: Man Sub
authors: MS
authors: Kim
authors: Yesol
authors: Y
authors: Bak
authors: Yun Sun
authors: YS
authors: Park
authors: Dong Hun
authors: DH
authors: Lee
authors: Jung Hee
authors: JH
authors: Kim
authors: Jeong Woo
authors: JW
authors: Kang
authors: Hyuk-Hwan
authors: HH
authors: Song
authors: Sei-Ryang
authors: SR
authors: Oh
authors: Do Young
authors: DY
authors: Yoon
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis* / Q000235:genetics; D030361:Papillomavirus Infections / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000821:virology
chemical_list: D004365:Drugs, Chinese Herbal; C068651:E6 protein, Human papillomavirus type 16; D044950:Flavanones; D005419:Flavonoids; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010936:Plant Extracts; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C085514:wogonin