Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines

• Published in: Toxics (Basel) Vol. 7; no. 3; p. 43
• Main Authors: Ribeiro, Edna, Delgadinho, Mariana, Brito, Miguel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.08.2019; MDPI
• Subjects: Apoptosis; Bcl-x protein; Bisphenol A; c-Fos protein; Cancer therapies; Carcinogenesis; Carcinogens; Cell culture; Cell cycle; Chemicals; Chemotherapy; Cyclin-dependent kinase inhibitor p21; Cyclin-dependent kinases; Dosage; Doxorubicin; drug interaction; Drug resistance; Estrogens; Exposure; Food contamination & poisoning; Gene expression; gene transcription; Hep-2 cell line; Ingestion; Kinases; MRC-5 cell line; Organs; Risk assessment; Statistical analysis; Transcription; United States > US; Bisphenol A; gene transcription; doxorubicin; MRC-5 cell line; Hep-2 cell line; drug interaction
• ISSN: 2305-6304; 2305-6304
• DOI: 10.3390/toxics7030043

The worldwide production of synthetic chemicals, including endocrine disruptor chemicals (EDCs), such as Bisphenol A (BPA) has increased significantly in the last two decades. Human exposure to BPA, particularly through ingestion, is continuous and ubiquitous. Although, considered a weak environmental estrogen, BPA can induce divergent biological responses through several signaling pathways, including carcinogenesis in hormone-responsive organs. However, and despite the continuous increase of tumor cell-resistance to therapeutic drugs, such as doxorubicin (DOX), information regarding BPA drug interactions is still scarce, although its potential role in chemo-resistance has been suggested. This study aims to assess the potential interactions between environmentally relevant levels of BPA and DOX at a therapeutic dosage on Hep-2 and MRC-5 cell lines transciptome. Transcriptional effects in key-player genes for cancer biology, namely , , and , were evaluated through qRT-PCR. The cellular response was analyzed after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis showed that BPA exposure induces upregulation of and endorses an antagonistic non-monotonic response on DOX transcriptional effects. Moreover, the BPA interaction with DOX on and expression emphasize its cellular specificity and divergent effects. Overall, Hep-2 was more susceptible to BPA effects in a dose-dependent manner while MRC-5 transcriptional levels endorsed a non-monotonic response. Our data indicate that BPA environmental exposure may influence chemotherapy outcomes, which emphasize the urgency for a better understanding of BPA interactions with chemotherapeutic agents, in the context of risk assessment.