DNA repair can prevent mutations and cancer development, target proteins or molecules involved in DNA repair mechanisms, and destroy cancer cells. Therefore, chemotherapeutic agents or bioactive components have been used to induce DNA damage and thus activate DNA repair pathways to treat cancer cells. Thus, inhibitors of DNA repair pathways can be developed by targeting molecules or signaling pathways that play a role in repair mechanisms. In this context, our study aimed to show the anticancer effect of the bioactive component pristimerin on C-4 I cervical cancer cells via the activation of DNA repair pathways. After isolating RNA from C-4 I cervical cancer cells treated with pristimerin (IC50=15 µM) for 24 hours, a sequencing library was constructed. After sequencing with the DNBEQ library (Species: Homo sapiens), KEGG pathways, Kegg network, cluster heatmaps and protein-protein interactions analyses were examined. Based on KEGG analysis of C-4 I_control/C-4 _IC50, we found that Base Excision Repair (BER; Q = 0.000002) was regulated by 20 genes, Mismatch Repair (MMR; Q = 0.00001) by 15 genes, Homologous Recombination (HR; Q =0.00008) by 20 genes, and Nucleotide Excision Repair (NER; Q = 0.0001) by 21 genes. Kegg network and Kegg map analysis revealed that these repair pathways interact with each other and share common signaling pathways and genes. Upon examining BER, we found that this pathway leads to necroptosis via PAPRP1 and HMGB1 genes and autophagy via HMGB1 gene, while HR induced cellular senescence via NBN gene. We also observed that MMR and NER affected the cell cycle respectively via PCNA gene, and CCNH and PCNA genes. The results indicated that pristimerin can induce various types of DNA damage, such as base excision, double-strand breaks, and nucleotide excision and the Failure to repair DNA damage led to cell death, cell cycle arrest and senescence. These findings hold promise for developing more specific treatments for cancer by targeting specific molecules in the damage repair pathways.

Souandaou Athoumani Ali recently graduated (2024 year) from Istanbul University with a PhD degree in cancer biology and bioinformatics at the age of 27, She has published articles in both national and international journals. She is an active member of the Molecular Cancer Association (MOKAD) and the European Association research cancer (EARC). She recently joined Bioinforage, an association of researchers in the field of biology. She is currently writing articles about her doctoral thesis and preparing herself for post-doctoral research. Her research fields include cancer, molecular biology, cell biology, medicinal plants, and bioinformatics.