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

Title
Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells
Author(s)
Kim, Man SubBak, YesolPark, Yun SunLee, Dong HunKim, Jung HeeKang, Jeong WooSong, Hyuk-HwanOh, Sei-RyangYoon, Do Young
Issued Date
2013-08
Citation
Cell Biology and Toxicology, v.29, no.4, pp.259 - 272
Type
Article
Author Keywords
ApoptosisAntitumorCervical cancerFlavonoid
Keywords
HUMAN-PAPILLOMAVIRUS TYPE-16SCUTELLARIA-BAICALENSISMEDIATED APOPTOSISCARCINOMA CELLSDOWN-REGULATIONIN-VIVOP53DEATHRECEPTORIMMORTALIZATION
ISSN
0742-2091
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. © 2013 Springer Science+Business Media Dordrecht.
URI
http://hdl.handle.net/20.500.11750/5305
DOI
10.1007/s10565-013-9251-4
Publisher
Springer
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