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

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.