Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer.

ABSTRACT

The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls p',p' dichloro diphenyl trichloroethane (DDT), p'p' dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of cancer in Indian women. Proteomic analysis of plasma from estrogen receptor-positive breast cancer patients revealed 17 dysregulated proteins, but transthyretin (TTR) was three times higher than in healthy controls, which is further validated by enzyme-linked immunosorbent assays (ELISA). Molecular docking and molecular dynamics studies revealed a competitive affinity between endosulfan II and the thyroxine-binding site of TTR, pointing towards the significance of the competition between thyroxin and endosulfan, resulting in endocrine disruption leading to breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on women's health.