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Transport carrier Abstract Tobacco smoking is the leading preventable cause of cancer.

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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.

Tobacco smoke extracts induced similar increases in cisplatin resistance.

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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.

Download PDF Introduction Head and neck squamous cell carcinoma HNSCC is the sixth most common malignancy, with overnewly diagnosed cases anddeaths per year worldwide 1.

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Despite improved treatment options, including targeted therapies, the prognosis fájdalom a bal lábujj ízületében HNSCC patients urine test for prostate cancer uk poor.

Thus, most head and neck tumors present as advanced disease, requiring combined modality approaches that frequently include radiotherapy and platinum-based chemotherapy, with or without surgery 34. Platinum-based chemotherapy consisting of either cisplatin or carboplatin is the usual first-line treatment for inoperable recurrent or metastatic HNSCC 5.

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In addition to late diagnosis, therapy resistance is one of the main factors contributing to poor cancer prognosis. Cisplatin resistance can emerge due to a host of environmental factors as well as genetic or epigenetic alterations in cancer cells 6. Tobacco smoking is the leading preventable cause of death and the main risk factor for lung and head and neck cancers.

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It is also well established that cigarette smoking has negative implications on cancer outcomes, including increasing disease progression, incidence of second primary tumors, and treatment-related toxicity, and reducing patient survival 7891011 Smoking at the time of diagnosis has been shown to increase resistance to radio- and chemo-therapy 713 and tumor recurrence 91114 urine test for prostate cancer uk, Concerned about the negative consequences of smoking but unable or unwilling to quit due to nicotine addiction, cancer patients, and urine test for prostate cancer uk in general, are increasingly seeking other methods of nicotine delivery.

Electronic cigarettes e-cigarettes are battery-operated devices that heat a solution of chemicals propylene glycol, glycerol, and flavorings with or without nicotine, to produce an inhalable aerosol.

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Studies have shown that e-cigarette aerosols contain harmful and potentially harmful toxicants such as volatile organic compounds e. Some e-cigarette aerosol components are carcinogenic or potentially carcinogenic e.

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Curiously, some of the individual constituents present in e-cigarette aerosols have been shown to increase chemotherapy sensitivity e. Yet, thanks to few restrictions and a lack of regulatory guidelines, e-cigarettes are aggressively marketed both as a safer alternative to combustible tobacco and as a smoking cessation aid.

Consequently, the use of e-cigarettes has increased exponentially since introduction into the U. More than 5.

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Among adults, current smokers had the highest rate of use, with These alarming numbers and the presence of harmful and potentially harmful chemicals in e-cigarette aerosols 24coupled with the paucity of short- and long-term studies on the safety of e-cigarettes, all stress the urgent need to investigate the potential effects of e-cigarettes on cancer treatment thoroughly.

E-cigarettes can deliver nicotine levels similar to those observed in smokers Nicotine, a main component of e-cigarette aerosol, has been shown to reduce cisplatin-induced cell death Other toxicants present in e-cigarette aerosols have also been shown to positively or negatively impact chemotherapy sensitivity.

Hence, we hypothesized that exposure to e-cigarette aerosol might alter cisplatin resistance.

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Here we show that exposure of oral cancer cells to e-cigarette aerosol extracts increases cisplatin resistance through nicotine-dependent and independent mechanisms.

Moreover, in vitro studies have demonstrated that cigarette smoke condensate and nicotine can increase cancer therapy resistance in diverse cancer cell lines, including those derived from HNSCC 28 Hence, it is essential to determine whether exposure to e-cigarette aerosols might modify cancer response to chemotherapy. To explore this important clinical question, we began by evaluating the effect of e-cigarette exposure on cell viability after cisplatin treatment.

Nicotine is the only tobacco smoke component with a well-documented role in cisplatin resistance To dissect the contribution of nicotine, within the complex e-cigarette aerosol mixture, to cisplatin resistance our study design included an extract without nicotine E0. For comparison, cancer cells were exposed to a similar dose of mainstream tobacco smoke MS extracts.

Cell viability was determined by MTT 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide assay.

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We also observed a comparable increase in cell viability after cisplatin treatment in cells exposed to MS smoke extracts Fig. Figure 1 Exposure to e-cigarette aerosol extracts reduces cisplatin-induced cell death and increases cell viability.

Viability was assessed by the MTT test and normalized to non-cisplatin treatment. Consistent with previous reports 36exposure to e-cigarette aerosol or tobacco smoke extracts alone, at the doses used in this study, did not increase cell growth Figure S1 a—c.

These findings suggest that the increase in cell viability observed after cisplatin treatment is not due to an increase in cell proliferation but instead to an increase in cisplatin resistance induced by the presence of e-cigarette aerosol extracts. To further understand the relationship between e-cigarette exposure, cisplatin treatment, and cell viability, we assessed the impact of e-cigarette aerosol extracts on cell death induced by cisplatin using the trypan blue exclusion method.

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Consistent with the cell viability results Fig. The observed reduction in cell death was similar for e-cigarette extracts with and without nicotine Fig. Collectively, these data show that in vitro exposure to e-cigarette aerosol does not change cell proliferation but significantly reduces cell death induced by cisplatin.

Remarkably, our data suggest that nicotine-independent mechanisms play a key role in the observed decrease in cisplatin-induced cell death.

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HNSCC cells were exposed to e-cigarette aerosol extracts for 48 h and treated for an additional 48 h with extracts and cisplatin 0. Compared to vehicle-exposed cells controlexposure to e-cigarette aerosol extracts significantly increased the cisplatin IC50 values for all extracts and cell lines Fig.

Consistent with the data shown in Fig. This suggests once again that the cisplatin dose—response effect on cell viability is independent of the amount of nicotine in the e-cigarette extracts.

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Likewise, the increase in IC50 observed in cells exposed to e-cigarette aerosol extracts was comparable to that observed in cells exposed to MS smoke extracts Fig. Overall, these results suggest that like tobacco smoke, exposure to e-cigarette aerosol increases the resistance of cancer cells to cisplatin. Moreover, it suggests that mechanisms independent of nicotine contribute to the cisplatin resistance induced by e-cigarettes.

Figure 2 Exposure to e-cigarette aerosol extracts increases IC Dose—response curves after exposure to e-cigarette aerosol or MS extracts and 0.