Abstract
BackgroundPersistent infection with high-risk human papillomavirus (hrHPV) is associated with cervical cancer development. This process involves the virus-encoded E6 and E7 oncoproteins, which are maintained and expressed during all malignant transformation stages. However, HPV alone is insufficient to drive tumor progression-related behaviors such as cervical cancer cell motility. In this study, we investigated the effect of phenyllactic acid (PLA), a phenolic acid phytochemical and biomarker for discriminating various cancers, on the metastatic potential of cervical cancer cells.MethodsThe effects of PLA on HPV16/18 E6/E7 expression, migratory and invasive behavior, and matrix metalloproteinases (MMPs) expression of cervical cancers cells were measured. Specific inhibitors were used to further investigate biological function and underlying mechanism of PLA modulated cell motility.ResultsPLA significantly promoted the migration and invasion of SiHa, HeLa, and C-33A cervical cancer cells as well as upregulated matrix metalloproteinase-9 (MMP-9) expression. Moreover, PLA treatment attenuated E6/E7 expression in SiHa and HeLa cells. Further molecular analysis showed that PLA activated the nuclear factor-kappa B (NF-κB) signaling pathway and increased the nuclear translocation of both IκBα and p65. Treating cervical cancer cells with an NF-κB inhibitor potently reversed PLA-induced migratory and invasive behavior, MMP-9 upregulation, and/or E6/E7 downregulation. The PLA-induced NF-κB activation and MMP-9 upregulation were mediated by IκB kinase-β (IKK-β) phosphorylation via PKC signals. The results suggested that SiHa, HeLa, and C-33A cells might undergo a similar process to enhance their motility in response to PLA, regardless of the HPV status.ConclusionsCollectively, our study reveals a new biological function of PLA and elucidate the possible molecular role of PLA as a risk factor for triggering cervical cancer cell motility.
Highlights
Persistent infection with high-risk human papillomavirus is associated with cervical cancer development
phenyllactic acid (PLA) inhibited E6/E7 expression and promoted the migration and invasion of cervical cancer cells To assess whether PLA has functional roles in the regulation of E6 and E7 expression in HPV16/18-integrated SiHa and HeLa cells or human papillomaviruses (HPVs)-negative C-33A cells, racemic DL-PLA was used at a concentration ranging from 2.5 to 20 mM, which is defined as a nontoxic concentration [13]
Our data suggested that millimolar concentrations of PLA can inhibit the expression of the HPV16/18 E6 and E7 oncoproteins and promote the in vitro migration and invasion of SiHa, HeLa, and C-33A cells
Summary
Persistent infection with high-risk human papillomavirus (hrHPV) is associated with cervical cancer development. This process involves the virus-encoded E6 and E7 oncoproteins, which are maintained and expressed during all malignant transformation stages. Lactobacillus is the predominant bacteria in healthy vagina and plays an vital role in protection of female reproduction system. It exerts its protective functions mainly via several mechanisms, including preventing pathogenic bacteria by acting as a barrier on the epithelial cells, activating the immune system, and secreting various metabolites and organic acid [6]. PLA was well documented to play a positive role during the progression of different cancers, its potential molecular mechanism has not been validated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
