Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells

Abstract Tobacco smoking is the leading preventable cause of cancer. Moreover, continued smoking during cancer therapy reduces overall survival. Aware of the negative consequences of tobacco smoking and the challenges of smoking cessation, cancer patients are inquiring whether they should switch to...

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Main Authors: Jimmy Manyanga, Vengatesh Ganapathy, Célia Bouharati, Toral Mehta, Balaji Sadhasivam, Pawan Acharya, Daniel Zhao, Lurdes Queimado
Format: Article
Language:English
Published: Nature Publishing Group 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-81148-0
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spelling doaj-777e74d2b872400796474d49449f5c9c2021-01-24T12:31:32ZengNature Publishing GroupScientific Reports2045-23222021-01-0111111410.1038/s41598-021-81148-0Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cellsJimmy Manyanga0Vengatesh Ganapathy1Célia Bouharati2Toral Mehta3Balaji Sadhasivam4Pawan Acharya5Daniel Zhao6Lurdes Queimado7Department of Otolaryngology Head and Neck Surgery, The University of Oklahoma Health Sciences CenterDepartment of Otolaryngology Head and Neck Surgery, The University of Oklahoma Health Sciences CenterDepartment of Otolaryngology Head and Neck Surgery, The University of Oklahoma Health Sciences CenterDepartment of Otolaryngology Head and Neck Surgery, The University of Oklahoma Health Sciences CenterDepartment of Otolaryngology Head and Neck Surgery, The University of Oklahoma Health Sciences CenterDepartment of Biostatistics and Epidemiology, The University of Oklahoma Health Sciences CenterDepartment of Biostatistics and Epidemiology, The University of Oklahoma Health Sciences CenterDepartment of Otolaryngology Head and Neck Surgery, The University of Oklahoma Health Sciences CenterAbstract Tobacco smoking is the leading preventable cause of cancer. Moreover, continued smoking during cancer therapy reduces overall survival. Aware of the negative consequences of tobacco smoking and the challenges of smoking cessation, cancer patients are inquiring whether they should switch to electronic cigarettes (e-cigarettes). To obtain evidence-based data to inform this decision, we examined the effects of e-cigarette aerosol exposure on cisplatin resistance in head and neck cancer cells. Our results show that cancer cells exposed to e-cigarette aerosol extracts and treated with cisplatin have a significant decrease in cell death, increase in viability, and increase in clonogenic survival when compared to non-exposed cells. Moreover, exposure to e-cigarette aerosol extracts increased the concentration of cisplatin needed to induce a 50% reduction in cell growth (IC50) in a nicotine-independent manner. Tobacco smoke extracts induced similar increases in cisplatin resistance. Changes in the expression of drug influx and efflux transporters, rather than activation of cell growth-promoting pathways or DNA damage repair, contribute to e-cigarette induced cisplatin resistance. These results suggest that like combustible tobacco, e-cigarette use might increase chemotherapy resistance, and emphasize the urgent need for rigorous evaluation of e-cigarettes health effects to ensure evidence-based public health policies.https://doi.org/10.1038/s41598-021-81148-0
collection DOAJ
language English
format Article
sources DOAJ
author Jimmy Manyanga
Vengatesh Ganapathy
Célia Bouharati
Toral Mehta
Balaji Sadhasivam
Pawan Acharya
Daniel Zhao
Lurdes Queimado
spellingShingle Jimmy Manyanga
Vengatesh Ganapathy
Célia Bouharati
Toral Mehta
Balaji Sadhasivam
Pawan Acharya
Daniel Zhao
Lurdes Queimado
Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
Scientific Reports
author_facet Jimmy Manyanga
Vengatesh Ganapathy
Célia Bouharati
Toral Mehta
Balaji Sadhasivam
Pawan Acharya
Daniel Zhao
Lurdes Queimado
author_sort Jimmy Manyanga
title Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
title_short Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
title_full Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
title_fullStr Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
title_full_unstemmed Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
title_sort electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-01-01
description Abstract Tobacco smoking is the leading preventable cause of cancer. Moreover, continued smoking during cancer therapy reduces overall survival. Aware of the negative consequences of tobacco smoking and the challenges of smoking cessation, cancer patients are inquiring whether they should switch to electronic cigarettes (e-cigarettes). To obtain evidence-based data to inform this decision, we examined the effects of e-cigarette aerosol exposure on cisplatin resistance in head and neck cancer cells. Our results show that cancer cells exposed to e-cigarette aerosol extracts and treated with cisplatin have a significant decrease in cell death, increase in viability, and increase in clonogenic survival when compared to non-exposed cells. Moreover, exposure to e-cigarette aerosol extracts increased the concentration of cisplatin needed to induce a 50% reduction in cell growth (IC50) in a nicotine-independent manner. Tobacco smoke extracts induced similar increases in cisplatin resistance. Changes in the expression of drug influx and efflux transporters, rather than activation of cell growth-promoting pathways or DNA damage repair, contribute to e-cigarette induced cisplatin resistance. These results suggest that like combustible tobacco, e-cigarette use might increase chemotherapy resistance, and emphasize the urgent need for rigorous evaluation of e-cigarettes health effects to ensure evidence-based public health policies.
url https://doi.org/10.1038/s41598-021-81148-0
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