Abstract
Tobacco smoke and human papillomavirus (HPV) are both crucial causes of cancer, and their cooperative carcinogenesis has drawn more attention in recent years. Apigenin (AP), a typical flavonoid abundantly found in flowers of plants, vegetables, and fruits, has been demonstrated to exert an anti-carcinogenic effect on various types of cancer. In this study, we investigated the capability of AP against malignant transformation and DNA damage of immortalized human esophageal epithelial (SHEE) cells induced by the synergism of HPV18 and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The results indicated that the enhancement of migration, invasion, and proliferation ability of SHEE cells induced by HPV and NNK could be effectively inhibited by AP. Moreover, the levels of pyridyloxybutylated (POB)-DNA adducts induced by NNK via P450-catalyzed metabolic activation could also be significantly suppressed by AP. Further analyses on the molecular mechanism revealed that AP inhibited the synergistic carcinogenesis of NNK and HPV on SHEE cells by reducing the expression of mutp53, CDK4, Cyclin D1, and p-Rb (Ser 780), increasing caspase-3 activity, thereby arresting the cell cycle at G1 phase and promoting apoptosis of SHEE cells. We hypothesize that the decrease in NNK-induced POB-DNA adduct levels is related to the deactivation of P450 by AP, which needs to be confirmed in future studies. This study highlights that AP may be employed as a promising chemopreventive agent against cancers in smokers with an HPV infection.
Highlights
Tobacco smoke is an important cause of cancer, contributing to 22% of all cancer deaths and 71%of lung cancer deaths worldwide [1]
We investigated the chemopreventive effect of AP on the inhibition of the synergism between NNK and human papillomavirus (HPV), which will assist in the prevention and treatment of cancers related to smoking and HPV infection
The literal migration of SHEE-E6E7 and SHEE-V cells treated by NNK and NNK + AP was monitored by cell scratch assays
Summary
Tobacco smoke is an important cause of cancer, contributing to 22% of all cancer deaths and 71%of lung cancer deaths worldwide [1]. Besides DNA damage induction, the carcinogenesis of NNK involved in protein regulation in cell cycle and apoptosis, such as cyclin D1, Bcl-2, and Bax, leading to cell proliferation or anti-apoptosis [6,7]. Viral infection is another important cause of cancer, which can cooperate with chemical carcinogens in the development of cancer. A number of epidemiological evidences indicate that the synergistic effect between tobacco smoke and hr-HPV shows associations with the occurrence and development of cervical cancer, as well as head and neck cancers [16,17,18,19,20]. It is necessary to elucidate the mechanism and explore possible chemoprevention of the synergism between NNK and hr-HPV
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
