Fig. 7.

Schematic of the pathways involved in punicalagin-induced autophagic degradation of E6 and E7. In human papillomavirus (HPV)-infected cervical cancer cells, the binding of BCL2 to BECN1 blocks its interaction with other components of the PIK3C3 complex that regulates autophagosome nucleation for membrane formation. Treatment with punicalagin promotes the production of reactive oxygen species (ROS), which leads to the activation and phosphorylation of JNK. Activated JNK directly phosphorylates BCL2. Phosphorylated BCL2 promotes the dissociation of the BECN1/BCL2 complex. BECN1 binds to the PIK3C3 complex and initiates autophagy. Accelerated autophagosome formation and autophagosome-lysosome fusion lead to the lysosomal degradation of its targets E6 and E7. This results in the suppression of cervical cancer cell proliferation and survival and the inhibition of tumor growth.