EGF induces SOD activity, TNF-α/IL-6 expression and complement regulatory proteins in cervical cancer cells: suppression by EGCG.

Human papilloma virus (HPV) infection is known to induce chronic inflammation and trigger oncogenesis. The present study is intended to understand the role of EGF on the secretion of inflammatory cytokines by CC and to assess the anti-inflammatory efficacy of EGCG under basal and EGF-stimulated conditions. EGCG inhibited the EGF-induced phosphorylation of EGFR at Y992 and AKT at S473 in CC cells. Further, we showed that EGCG is capable of inhibiting the proliferation in 2D and elevating apoptosis in 2D and 3D spheroid culture via increased ROS generation and decreasing SOD enzymatic activity in both HPV positive ME180 and HPV negative C33A cells under basal and EGF-stimulated conditions. The mRNA expression of SOD1/2 along with their enzymatic activity, tumor necrosis factor-α (TNF-α) and programmed death-ligand 1 (PD-L1) transcripts was found to be downregulated by EGCG. The increase in inflammatory markers such as interleukin 6 (IL-6), C reactive protein (CRP) and TNF-α were elevated upon EGF treatment. The critical contributing molecules produced by CC cells that are reported to engage immune cells such as CD46, CD55 and CD59 levels are downregulated by EGCG. Pre-treatment with EGCG blocked EGF-induced changes in CC cells. Collectively, these findings indicate the inflammatory role for EGF and attest the anti-inflammatory potential of EGCG in CC cells.