Ethyl β-carboline-3-carboxylate targets PRDX5/c-Jun axis for novel therapeutic strategy against cervical cancer

Abstract

Objective Cervical cancer remains a significant global health challenge, with conventional therapies often proving inadequate due to treatment resistance and adverse effects. This study investigates the therapeutic potential of ethyl β-carboline-3- carboxylate (β-CCE) in cervical cancer and elucidates its molecular mechanism through peroxiredoxin 5 (PRDX5) modulation. Methods Western blot assay were performed to asses the expression of protein levels; The cellular and mitochondrial ROS and mithochondrial membrane potential were observed with fluorescence microscopy; Bioinformatics analysis were used to check the expression levels of PRDX5 and JUN family proteins and prognosis analysis in cervical cancer; Transcriptome analysis was performed to analyse the gene expression levels between mock and shPRDX 5 cells; Serum TNF-α and INF-γ levels were detected by ELISA kits; HE staining analysis were performed to check the organ histopathological changes in mice. Results This effect is mediated through activation of the MAPK signaling cascade, particularly involving P38, ERK, and JNK pathways. Notably, β-CCE treatment promotes apoptosis through c-Jun up-regulation, with PRDX5 knockdown enhancing this effect while its overexpression provides protection. In xenograft mouse models, β-CCE treatment significantly suppressed tumor growth and enhanced anti-tumor immune responses, particularly in PRDX5-depleted conditions, without apparent systemic toxicity. The therapeutic efficacy was evidenced by reduced tumor volume (65.3%) and elevated levels of immunological markers (IFN-γ and TNF-α). Conclusion These findings establish PRDX5 as a critical therapeutic target in cervical cancer and demonstrate β-CCE potential as a novel treatment strategy through its dual mechanism of direct tumor cell apoptosis and immune response modulation. Our study provides compelling evidence for the development of PRDX5-targeted therapies using β-CCE as a promising therapeutic agent for cervical cancer treatment.