Interaction between environmental pollutants and cancer drug efficacy: Bisphenol A, Bisphenol A diglycidyl ether and Perfluorooctanoic acid reduce vincristine cytotoxicity in acute lymphoblastic leukemia cells

Abstract

Every day, we are exposed to many environmental pollutants that can enter our body through different routes and cause adverse effects on our health. Epidemiological studies suggest that these pollutants are responsible for approximately nine million deaths per year. Acute lymphoblastic leukemia (ALL) represents one of the major cancers affecting children, and although substantial progress has been made in its treatment, relapses are frequent after initial treatment and are now one of the leading causes of cancer-related death in pediatric patients. Currently, relatively little attention is paid to pollutant exposure during drug treatment and this is not taken into account for dose setting or regulatory purposes. In this work, we investigated how bisphenol A (BPA), its derivative bisphenol A diglycidyl ether (BADGE), and perfluorooctanoic acid (PFOA) alter vincristine treatment in ALL when administered before or together with the drug. We found that these three pollutants at nanomolar concentrations, lower than those established by current regulations, can reduce the cytotoxic effects of vincristine on ALL cells. Interestingly, we found that this is only achieved when exposure to pollutants occurs prior to administration of the chemotherapeutic drug. Moreover, we found that this effect could be mediated by activation of the PI3K/AKT pathway and stabilization of microtubules. This work strengthens the idea of starting to take into account exposure to pollutants to improve the efficacy of chemotherapy treatments.

STAT3 Pathways Contribute to β-HCH Interference with Anticancer Tyrosine Kinase Inhibitors

“…The response of a human organism to a specific therapy is often estimated without considering the drug’s interaction with other xenobiotic compounds, i.e., environmental pollution. As supported by well-established scientific evidence, chemical carcinogenesis may contribute to, or even be responsible for, the phenomenon of chemoresistance [ 46 ]. Examining the mechanisms that induce acquired resistance, it was hypothesized that compounds capable of activating cellular responses such as proliferation and the activation of oncogenic and anti-apoptotic pathways may contribute to predisposing cancer cells to non-sensitivity to chemotherapy.…”

Synthetic Lethality Approaches in Acute Lymphoblastic Leukemia

“…Leukemia constitutes a collective term for a diverse group of malignant disorders characterized by the excessive production of abnormal cells in hematopoietic tissues, such as bone marrow and the lymphatic system [1][2][3]. The classification of leukemias encompasses several types, which are distinguished mainly by the speed of growth-acute (fast) or chronic (slower)-and the type of cell originating, either myeloid (giving rise to erythrocytes, platelets, monocytes, neutrophils, basophils and eosinophils) or lymphoid (giving rise to T lymphocytes, B lymphocytes and NK cells) [4][5][6].…”