Unveiling BPDE Induced Carcinogenic Signaling: Computational Insights into NF-κB, MAPK, and PI3K/Akt Pathway Activation

Abstract The Carcinogen benzo[a]pyran-7, 8 dihydrodiol 9, 10 epoxide(BaP-DNP) the active metabolite of benzo[a]pyrene has been postulated to induce carcinogenesis through formation of adduct with DNA and through alteration of critical pathways involved in signaling. Besides genotoxicity, BPDE has more recently been reported to alter the NF-κB, MAPK, and PI3K/Akt, that are involved in inflammation, cell survival and cell proliferation. From the above molecular docking analysis of BPDE binding to the potential proteins of these pathways, the mechanism of action of the compound is examined. The studies conducted on docking reveal moderate binding affinity of BPDE with NF-κB, that is, -6.11 kcal/mol, which points out its role in inflammation and oncogenic signaling. In addition, BPDE has more protein-binding affinities within the MAPK and PI3K/Akt pathway for CDK1 (-7.46 kcal/mol), LOX (-7.47 kcal/mol), and CDK6 (-6.84 kcal/mol). These indicate that influence of BPDE in tumour progression should not be only through the activation of NF-κB but would rather be supported by significant inputs of pathways that include PI3K/Akt and MAPK. This interaction would seem to favor cell survival, proliferation, and apoptosis resistance. Broader analysis of the data presented allows defining NF-κB as one of the key molecules contributing to BPDE-induced carcinogenesis; however, the data also point to the significant participation of the MAPK and PI3K/Akt pathways in this process. Future work should also more fully detail how these pathways interconnect and also evaluate the effectiveness of inhibiting NF-κB and related pathways in preventing BPDE’s carcinogenic action. This study adds to understanding of molecular mechanisms and therapeutic targets of BPDE. Competing Interest Statement The authors have declared no competing interest.