Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines
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 environment...
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doaj-5a71b6eae77f4e2dafd83732c60a68bf2020-11-25T01:36:06ZengMDPI AGToxics2305-63042019-08-01734310.3390/toxics7030043toxics7030043Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell LinesEdna Ribeiro0Mariana Delgadinho1Miguel Brito2H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisbon, PortugalH&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisbon, PortugalH&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisbon, PortugalThe 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 <i>c-fos</i>, <i>p21</i>, and <i>bcl-xl</i>, 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 <i>bcl-xl</i> and endorses an antagonistic non-monotonic response on DOX transcriptional effects. Moreover, the BPA interaction with DOX on <i>c-fos</i> and <i>p21</i> 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.https://www.mdpi.com/2305-6304/7/3/43Bisphenol AdoxorubicinHep-2 cell lineMRC-5 cell linedrug interactiongene transcription |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Edna Ribeiro Mariana Delgadinho Miguel Brito |
spellingShingle |
Edna Ribeiro Mariana Delgadinho Miguel Brito Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines Toxics Bisphenol A doxorubicin Hep-2 cell line MRC-5 cell line drug interaction gene transcription |
author_facet |
Edna Ribeiro Mariana Delgadinho Miguel Brito |
author_sort |
Edna Ribeiro |
title |
Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines |
title_short |
Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines |
title_full |
Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines |
title_fullStr |
Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines |
title_full_unstemmed |
Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines |
title_sort |
environmentally relevant concentrations of bisphenol a interact with doxorubicin transcriptional effects in human cell lines |
publisher |
MDPI AG |
series |
Toxics |
issn |
2305-6304 |
publishDate |
2019-08-01 |
description |
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 <i>c-fos</i>, <i>p21</i>, and <i>bcl-xl</i>, 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 <i>bcl-xl</i> and endorses an antagonistic non-monotonic response on DOX transcriptional effects. Moreover, the BPA interaction with DOX on <i>c-fos</i> and <i>p21</i> 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. |
topic |
Bisphenol A doxorubicin Hep-2 cell line MRC-5 cell line drug interaction gene transcription |
url |
https://www.mdpi.com/2305-6304/7/3/43 |
work_keys_str_mv |
AT ednaribeiro environmentallyrelevantconcentrationsofbisphenolainteractwithdoxorubicintranscriptionaleffectsinhumancelllines AT marianadelgadinho environmentallyrelevantconcentrationsofbisphenolainteractwithdoxorubicintranscriptionaleffectsinhumancelllines AT miguelbrito environmentallyrelevantconcentrationsofbisphenolainteractwithdoxorubicintranscriptionaleffectsinhumancelllines |
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