N-Benzylcinnamide induces apoptosis in HPV16 and HPV18 cervical cancer cells via suppression of E6 and E7 protein expression.
Seventy percent of all cervical cancers are caused by human papillomavirus (HPV) infections. Natural products are being extensively explored for their potential ability to prevent and treat cervical cancers. N-benzylcinnamide (PT-3) is a natural product purified from Piper submultinerve. Whether or not PT-3 has an effect on cervical cancer cells is as yet unknown. Therefore, we set out to explore the mechanism of action behind PT-3 and how it affects cells that either contain or lack HPV DNA. Our results demonstrate that PT-3 slows the growth kinetics of CaSki (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner, but does not slows HPV-negative cells. Importantly, we also found that PT-3 induces apoptosis by suppressing expression of E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and HeLa cells. Moreover, we found that suppression of E6 and E7 expression leads to modulations in p53 and protein retinoblastomas, which are not changed in HPV-negative cervical cancer C33A cells. These findings demonstrate that PT-3 can effectively promote apoptosis by downregulating expression of E6 and E7.
Department of Obstetrics and Gynecology, Jiangxi Provincial People's Hospital, Donghu District, Nanchang City, Jiangxi Province, China.
Yuanhuan
Y
Xiong
Faculty of Medical Sciences, Wuhan University School of Medicine, Wuhan, Hubei, People's Republic of China.
Lin
L
Chen
Department of Obstetrics and Gynecology, Jiangxi Provincial People's Hospital, Donghu District, Nanchang City, Jiangxi Province, China.
Puying
P
Luo
D017209:Apoptosis / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D002934:Cinnamates; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; C586180:N-benzylcinnamide; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
E6; E7; N-benzylcinnamide; apoptosis; cervical cancers; human papillomavirus