Colorectal cancer (CRC) remains a significant global health burden, with growing evidence highlighting microbial contributions to its pathogenesis. Certain genotoxigenic bacteria, such as Escherichia coli, Campylobacter jejuni, and Helicobacter pylori, produce virulence factors that induce DNA damage, genomic instability, and chronic inflammation—key features of carcinogenesis. At the same time, viruses such as JC polyomavirus (JCPyV), considered potentially oncogenic, and established oncogenic viruses like Epstein–Barr virus (EBV) and human papillomavirus (HPV) have been detected in colorectal tissues and are linked to cell cycle regulation, apoptosis, and DNA repair through their viral proteins. Intriguingly, recent findings suggest that bacterial genotoxins may promote the reactivation or transcriptional activity of persistent viruses such as JCPyV and EBV, possibly through DNA damage-induced stress and activation of NF-κB- or ATM-dependent signaling pathways. Despite these advances, interactions between oncogenic viruses and bacteria within the colon microbiome remain underexplored. This review integrates current evidence and provides future perspectives for addressing potential genotoxic collaboration between bacteria and viruses that could contribute to colorectal tumorigenesis. Elucidating these interactions could reveal novel biomarkers and therapeutic targets for the prevention and treatment of CRC.

The multidrug resistance (MDR) phenotype, mediated by transporters such as MDR1/P-glycoprotein (P-gp), represents a critical obstacle in the treatment of glioblastoma (GB). Natural antioxidants such as glycosylated delphinidins—anthocyanins abundant in Chilean berries, particularly the native species Aristotelia chilensis (maqui)—have emerged as bioactive compounds that modulate inflammation and cancer-related pathways. In this context, the regulation of inflammation-associated signaling pathways, including COX-2 and NF-κB, represents a potential strategy to overcome chemoresistance. In this study, we evaluated the effect of delphinidin-3-glucoside (DEL-3) on the COX-2/PGE₂ axis, MDR1 expression, and sensitivity to chemotherapeutic agents in U87-MG and GBM38 glioblastoma cells and in an NOD-SCID xenograft model using ELISA, RT-qPCR, Western blot, and luciferase reporter assays. DEL-3 reduced PGE₂ production, consistent with functional modulation of the COX-2/PGE₂ pathway, and downregulated MDR1 expression at both transcriptional and protein levels, in agreement with reduced promoter activity. Functionally, combined treatment with DEL-3 and MDR1-substrate chemotherapeutic agents enhanced cytotoxicity in U87-MG cells. Although DEL-3 did not significantly reduce tumor growth in a NOD-SCID xenograft model, MDR1 expression was reduced in treated tumors, indicating in vivo modulation of the target. Overall, these findings suggest that DEL-3, as a natural antioxidant, modulates inflammation-associated mechanisms and downregulates MDR1, thereby potentially enhancing the sensitivity of glioblastoma cells to MDR1-substrate chemotherapeutic agents.