Benzo[a]pyrene reduces cellular senescence in ovarian cancer by stabilizing c-Myc independently of DNA damage

Benzo[a]pyrene (BaP), a widespread environmental pollutant produced by the incomplete combustion of organic materials and cigarette smoke, has been linked to the promotion of cancer progression. In this study, we demonstrated that BaP not only enhances cisplatin resistance but also suppresses cellular senescence. Importantly, these effects occur independently of DNA damage. Mechanistically, BaP binds to the Thr58 site of c-Myc, preventing its phosphorylation at this residue. This interaction reduces c-Myc ubiquitination, resulting in its stabilization and increased oncogenic activity. The accumulation of c-Myc subsequently drives the expression of genes associated with tumor growth, metastasis, and drug resistance. Our findings uncover a novel mechanism through which environmental pollutants like BaP influence cancer biology, offering a theoretical basis for the prevention and management of such exposures. This research highlights the critical role of environmental factors in cancer development and identifies potential therapeutic targets to counteract the effects of these harmful compounds.