Effects of cigarette smoke extract derived from heated tobacco products on the proliferation of lung cancer stem cells

Hirata, Naoya; Horinouchi, Takahiro; Kanda, Yasunari

doi:10.1016/j.toxrep.2022.06.001

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Several reports indicate that extracts from the CSE derived from IQOS exhibit lower cytotoxicity than traditional tobacco [23][24][25]. In addition, there are a few reports that heated tobacco caused cell proliferation, and there is also a report that CSE contributed to proliferation [26][27][28]. However, the mechanisms of cytotoxicity and cell proliferation brought about by HTPs were not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2

Kagemichi,

Umemura,

Ishikawa

et al. 2024

J Physiol Sci

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Background The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco’s mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. Methods A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. Results CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. Conclusion Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2

Kagemichi,

Umemura,

Ishikawa

et al. 2024

J Physiol Sci

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“…With respect to the articles identified that described in vitro toxicological analyses of HTPs, articles were excluded from detailed discussion in this section of the review if they did not detail a direct quantitative comparison between the HTP(s) under investigation and other nicotine-or tobacco-containing products such as cigarettes and/or EVPs (i.e., statistical analyses were reported solely between the effects of the HTP and the negative control used) [64,65]; investigated any cell line not related to tissues of the oral cavity, respiratory tract, cardiovascular system or pluripotent stem cells [66][67][68][69][70][71][72]; attempted to investigate different human exposure scenarios using the same experimental methodology (i.e., sidestream smoke released by cigarettes being compared to aerosol produced by an HTP as a means of comparing bystander exposure between products) [67].…”

Section: In Vitro Toxicologymentioning

confidence: 99%

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

Cordery,

Thompson,

Stevenson

et al. 2024

Cureus

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Heated tobacco products represent a novel category of tobacco products in which a tobacco consumable is heated to a temperature that releases nicotine from the tobacco leaf but not to a temperature sufficient to cause combustion. Heated tobacco products may therefore have the potential to be a less harmful alternative for adult smokers who would otherwise continue to smoke cigarettes, as their use should result in exposure to substantially fewer and lower levels of toxicants. This update represents a two-year extension to our previous narrative review, which covered peer-reviewed journal articles published up to August 31, 2021. The scientific evidence published between 2021 and 2023 continues to indicate that aerosols produced from heated tobacco products contain fewer and substantially lower levels of harmful and potentially harmful constituents and that these observed reductions consistently translate to reduced biological effects in both in vitro and in vivo toxicological studies. Biomarker and clinical data from studies in which product use is controlled within a clinical setting continue to suggest changes in levels of biomarkers of exposure, biomarkers of potential harm, and clinical endpoints indicating the potential for reduced harm with switching to exclusive use of heated tobacco products in adult smokers. Overall, the available peer-reviewed scientific evidence continues to indicate that heated tobacco products offer promise as a potentially less harmful alternative to cigarettes, and as such, the conclusions of our original narrative review remain valid.

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“…Le prove attuali sono insufficienti per determinare se gli HTP siano meno dannosi delle sigarette combustibili e possano rappresentare un'alternativa nei fumatori persistenti con tumore ai polmoni. Hirata e coll [46]. hanno analizzato gli effetti dell'estratto di fumo di sigaretta da HTP sulle cellule staminali del tumore del polmone.…”

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Lung cancer smokers: quit smoking is a component of treatment

Perriot,

Rude-Bache

2024

Tabaccologia

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Nel 2020 il tumore al polmone è stata la principale causa di morte per tumori, con una stima di 1,8 milioni di decessi (18% dei decessi per tumore). Il fumo di tabacco è la causa del 90% dei tumori polmonari. Nonostante i progressi nel trattamento del tumore al polmone, il controllo del tabacco rimane la misura più efficace per frenare l'epidemia di tumore al polmone. Smettere di fumare, in tutte le fasi del processo tumorale, è associato a benefici in termini di guarigione, aumento dell'aspettativa di vita e della qualità della vita per i pazienti, riduzione delle complicanze mediche, chirurgiche e di terapia intensiva. Riduce i rischi di recidiva e di secondo tumore primario. Le farmacoterapie per smettere di fumare combinate con il supporto psicologico facilitano la cessazione del fumo. Smettere di fumare è una componente essenziale del trattamento del tumore al polmone. È necessaria la ricerca sui metodi migliori per gestire la cessazione del fumo nei pazienti affetti da tumore al polmone. Gli operatori sanitari coinvolti nella cura dei pazienti oncologici devono essere formati nel supporto per smettere di fumare.Parole chiave: tumore del polmone, trattamento del tumore, fumo di sigaretta, gestione della cessazione del fumo.

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Effects of cigarette smoke extract derived from heated tobacco products on the proliferation of lung cancer stem cells

Cited by 4 publications

References 21 publications

Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2

Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

Lung cancer smokers: quit smoking is a component of treatment

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