Comparative Effects of Cigarette Smoke and E-Cigarette Vapor on Oral Squamous Cell Carcinoma: Unraveling Distinct Molecular Pathways.

Dental research and oral health Pub Date : 2025-01-01 Epub Date: 2025-09-08 DOI:10.26502/droh.0098
Ryan Kinney, Logan Ponder, Neha Patel, Ankita Chatterjee, Kristina Vu, Harishma Sidhu, Benjamin Bikman, Paul R Reynolds, Juan A Arroyo
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Abstract

Oral squamous cell carcinoma (OSCC) poses a significant global health burden, driven by cigarette smoking and complicated by the rising popularity of e-cigarettes. This study compares the effects of cigarette smoke extract (CSE) and e-cigarette vapor extract (EVE) on OSCC progression using Ca9-22 gingival OSCC cells. CSE significantly increased cell invasion by upregulating the receptor for advanced glycation end-products (RAGE), nuclear factor kappa B (NF-κB), and matrix metalloproteinases (MMP-9, MMP-13), facilitating extracellular matrix degradation and metastasis. Conversely, the effects of EVE varied by flavor and nicotine content. Red Hot EVE (cinnamaldehyde-based) enhanced invasion and NF-κB levels with nicotine while reducing MMP-9 expression, suggesting alternative invasion pathways via MMP-13. Green Apple EVE had a less pronounced impact, indicating flavor-specific bioactivity. These findings reveal distinct mechanisms: CSE drives RAGE-NF-κB-MMP-mediated invasion, whereas EVE elicits variable, flavor-dependent responses, potentially involving nicotinic acetylcholine receptors. Targeted therapies, such as RAGE or NF-κB inhibitors, could mitigate tobacco-related OSCC progression. With e-cigarette use surging among youth, stricter regulations on flavored products and robust public health campaigns are urgently needed. Future research should investigate chronic exposures and diverse OSCC models to refine clinical and regulatory approaches, addressing the evolving landscape of tobacco-related oral cancers.

香烟烟雾和电子烟蒸汽对口腔鳞状细胞癌的比较影响:揭示不同的分子途径。
口腔鳞状细胞癌(OSCC)造成了重大的全球健康负担,由吸烟驱动,并因电子烟的日益普及而复杂化。本研究比较了香烟烟雾提取物(CSE)和电子烟蒸汽提取物(EVE)对Ca9-22牙龈OSCC细胞的OSCC进展的影响。CSE通过上调晚期糖基化终产物受体(RAGE)、核因子κB (NF-κB)和基质金属蛋白酶(MMP-9、MMP-13),促进细胞外基质降解和转移,显著增加细胞侵袭。相反,EVE的效果因口味和尼古丁含量而异。红热EVE(肉桂醛基)增强尼古丁的侵袭和NF-κB水平,同时降低MMP-9的表达,提示通过MMP-13有其他侵袭途径。青苹果EVE的影响不太明显,表明其具有特定风味的生物活性。这些发现揭示了不同的机制:CSE驱动RAGE-NF-κ b - mmp介导的入侵,而EVE引发可变的、风味依赖的反应,可能涉及尼古丁乙酰胆碱受体。靶向治疗,如RAGE或NF-κB抑制剂,可以缓解烟草相关的OSCC进展。随着电子烟在年轻人中的使用激增,迫切需要对调味产品实施更严格的监管,并开展强有力的公共卫生运动。未来的研究应该调查慢性暴露和不同的OSCC模型,以完善临床和监管方法,解决烟草相关口腔癌的发展前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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