Green Tea Polyphenols Cause Apoptosis and Autophagy in HPV-16 Subgene-Immortalized Human Cervical Epithelial Cells via the Activation of the Nrf2 Pathway.

Infection with human papillomavirus (HPV) is relatively common and certain high-risk HPV strains can induce epithelial dysplasia, increasing the risk of cervical cancer. Green tea polyphenol (GTP) preparations exhibit diverse anti-inflammatory, antioxidative, and antitumor properties In Vitro and In Vivo. Topical GTP application has been recommended as a treatment for genital warts, but the effect of GTP treatment on HPV infection and HPV-associated cancer remains to be established. The present study aimed to explore the mechanism by which GTP affected HPV type 16 (HPV-16)-positive immortalized human cervical epithelial cells. Survival, apoptosis, and autophagocytosis of these cells following GTP treatment was assessed using CCK-8 assay, flow cytometry, and monodansylcadaverine (MDC) staining. These cells were further transfected with an shRNA specific for Nrf2 to generate stable Nrf2-knockdown cells. The levels of Caspase-3, Bcl-2, Bax, P53, Rb, HPV-16 E6, HPV-16 E7, P62, Beclin1 and LC3B were determined via Western blotting. These analyses revealed that GTP treatment induced autophagy and apoptosis in HPV-16-positive cells, while Nrf2 gene knockdown reversed GTP-induced autophagic and apoptotic effects. Together, these results suggested that GTP could alleviate HPV infection and HPV-associated precancerous lesions In Vitro by regulating the Nrf2 pathway, highlighting the therapeutic potential of GTP in treating HPV infection.

Lycium barbarum polysaccharide protects HSF cells against ultraviolet-induced damage through the activation of Nrf2.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is considered an antioxidant agent. NF-E2-related factor-2 (Nrf2) is an important regulator for protection against UV damage. In this study, we verified the performance of LBP and the correlation between LBP and Nrf2. METHODS: HSF cells were treated with LBP to determine dose and time dependencies. An antioxidant response element (ARE) reporter was designed to monitor the activity of the Nrf2 antioxidant pathway. RESULTS: For HSF cells, the optimal LBP treatment was 300 µg/ml for 3 h. The ARE-reporter assay showed that LBP could increase the robustness of p-Nrf2. Treatments with genistein and LY294002 reduced of nuclear p-Nrf2 after 24 h. LBP increased the level of nuclear Nrf2, which functions by both phosphorylation and nuclear translocation. Silencing Nrf2 led to increased reactive oxygen species (ROS) levels, lower cell viability, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSP-PX) levels. This induced a higher level of lipid peroxide (LPO). However, LBP could decrease the levels of ROS and LPO and enhance the levels of SOD and GSP-PX. CONCLUSION: LBP protects HSF cells against UV damage via the regulation of Nrf2.