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Multi-Center “Replica Study” Challenges the Impact of Electronic Cigarette Aerosols on Cisplatin Resistance in Head and Neck Cancer Cells

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We wish to thank the Center of Excellence for the Acceleration of Harm Reduction (CoEHAR, University of Catania, Italy- COE01-05) for assisting our project with the resources provided.

R. Emma, G. Carota, K. Partsinevelos, S. Rust, A. Sun, A. Giordano, V. Volarevic, R. Lesmana, H. Goenawan, M. I. Barliana, A. Arsenijevic, N. Kastratovic, B. Spasic, Chiara Giardina, Miriana Cantali, R. Polosa, M. Caruso, G. Li Volti

Abstract

Background Cisplatin chemoresistance is a critical challenge in the treatment of head and neck squamous cell carcinoma (HNSCC). Since previous research has suggested that nicotine and e-cigarette (e-cig) aerosol might increase cisplatin resistance in oral cancer cells, this multicenter replication study aimed to replicate the work by Manyanga et al. (2021) and evaluate the oncologic implications of e-cigarette exposure during chemotherapy.

Methods This in vitro study involved standardized and harmonized protocols in international laboratories to examine the effects of cigarette smoke (1R6F) and e-cig aerosols with different concentrations of nicotine (0, 12, and 20 mg/ml nicotine) on cisplatin sensitivity in HNSCC cell lines (SCC-25, FaDu, and UM-SCC-1). Aerosols from 1R6F smoke and e-cig vapor were collected using a smoking and vaping machine, following ISO20778:2018 and ISO20768:2018 puffing regimes. The smoke and vapor were collected in PBS and diluted to 10 puffs/5L for HNSCC cell treatment. Chemosensitivity, clonogenicity, expression of gene for repair of cisplatin-induced DNA damage and gene and protein expression of cisplatin transporters were assessed by MTS, NRU, trypan blue, PCR, and Western blot assays, respectively.

Results Contrary to previous findings, exposure to e-cig aerosols did not significantly modulate cisplatin sensitivity in all cell lines. IC50 values, cytotoxicity assays, and clonogenic survival rates remained similar between e-cig treatments and cisplatin alone. Analysis of gene and protein expression revealed sporadic changes in the levels of transporters and repairs of cisplatin-induced DNA damage.

Conclusions This study did not fully substantiate previous claims of increased cisplatin resistance due to e-cigarette aerosols and nicotine. The variability in gene and protein expression among different cell lines underscores the need for cautious interpretation and further investigation of the role of e-cigarette components in cancer treatment. These findings provide a critical perspective for shaping public health policies and clinical practices related to e-cigarette use during chemotherapy.