Wogonin induces G1 phase arrest through inhibiting Cdk4 and cyclin D1 concomitant with an elevation in p21Cip1 in human cervical carcinoma HeLa cells.
Wogonin, a naturally occurring flavonoid, has been shown to have tumor therapeutic potential both in vitro and in vivo. To better understand its anticancer mechanism, we examined the effect of wogonin on human cervical carcinoma HeLa cells. In this study, we observed that G1 phase arrest was involved in wogonin-induced growth inhibition in HeLa cells. Over a 24 h exposure of HeLa cells to 90 micromol x L(-1) wogonin, the promoters of G1-S transition, including cyclin D1/Cdk4 and pRb, decreased within 12 h and E2F-1 depleted in the nucleus at the same time. As the G1 phase arrest developed, p53 and the Cdk inhibitor p21Cip1 elevated both at protein and mRNA levels. Furthermore, the up-regulation of p21Cip1 induced by wogonin was dramatically inhibited by siRNA-mediated p53 gene silencing. Collectively, our data suggested that wogonin induced G1 phase arrest in HeLa cells by modulating several key G1 regulatory proteins, such as Cdk4 and cyclin D1, as well as up-regulation of a p53-mediated p21Cip1 expression. This mechanism of wogonin may play an important role in the killing of cancerous cells and offer a potential mechanism for its anticancer action in vivo.
Yang
Li
L
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Zhang
Hai-wei
HW
Hu
Rong
R
Yang
Yong
Y
Qi
Qi
Q
Lu
Na
N
Liu
Wei
W
Chu
Yi-yi
YY
You
Qi-dong
QD
Guo
Qing-long
QL
D017209:Apoptosis / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; D044950:Flavanones; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; C085514:wogonin