Abstract

Abstract Background and Purpose: With the rising popularity of E-cigarettes among the youth, there is an urgent need to understand their long-term health implications, particularly the potential for carcinogenesis. Although tobacco smoking is established as a major cancer risk factor, the carcinogenic potential of E-cigarettes remains underexplored. Given that metastatic cancer accounts for most cancer-related deaths in the United States, elucidating the biological impacts of E-cigarette aerosols on cancer progression is critical for developing effective interventions. This study aims to address this critical gap by exploring the effects of E-cigarette aerosols on cellular models pertinent to breast and lung cancer. Methods: Mouse breast epithelial cells (HC11), triple-negative breast cancer cells (4T1), and human lung adenocarcinoma cells (Calu-3) were exposed to E-cigarette aerosol at the air-liquid interface for one hour, followed by a 24-hour recovery period. Results: Our study revealed that E-cigarette aerosols with mint flavor induce epithelial-to-mesenchymal transition (EMT) in both normal mammary epithelial and breast cancer cells. Furthermore, we also observed activation of the TGF pathway and an increased expression of stemness-related markers (OCT4, SOX2, NANOG, KLF4, and c-MYC) in 4T1 cells exposed to mint and menthol-flavored E-cigarette aerosols in both 2D and 3D cell culture environments. Microscopic examination at a 10X magnification level revealed that 4T1 and Calu-3 cells exposed to menthol-flavored E-cigarette aerosols exhibited signs of cellular disassociation and detachment whereas the control cells maintained discoidal aggregate morphology. Conclusion: The data presented here illuminate a potential link between E-cigarette use and carcinogenic processes, challenging the notion of E-cigarettes as a safe smoking alternative. This research is of paramount importance to cancer research as it unveils possible new avenues for tumor progression, emphasizing the necessity for a critical evaluation of E-cigarette products. Citation Format: Rizwana Begum, Shilpa Thota, Naveen Chintala, Biplov Sapkota, Abhishek Pandit, Joseph Francis. Carcinogenic influence of e-cigarette aerosols on breast and lung cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 210.

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