Li Yi-Chen, Cheng Ann-Joy, Lee Li-Yu, Huang Yu-Chen, Chang Joseph Tung-Chieh
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
J Cancer. 2019 Jul 8;10(17):4054-4062. doi: 10.7150/jca.29765. eCollection 2019.
Oral cancer is one of the most frequent malignant diseases worldwide, and areca nut is a primary carcinogen causing this cancer in Southeast Asia. It has been widely reported that areca nut induced several cytotoxic effects in oral cells, including ROS generation, inflammation, tissue hypoxia, DNA damage, and cell invasion. Recently, through chronic exposure model, more extensive pathological effects due to areca nut have been found. These include the induction of autophagy, promotion of epithelial- mesenchymal transition, and facilitation of cancer stemness conversion. Clinical findings support these adverse effects. Oral submucosal fibrosis, a premalignant condition, is prevalent in the area with habitual chewing of areca nuts. Consistently, oral cancer patients with habitual chewing areca nut exhibit more aggressive phenotypes, including resistance to chemo-radiotherapy. In this review, we comprehensively discuss and concisely summarize the up-to-date molecular and cellular mechanisms by which areca nuts contribute to malignant transformation. This review may provide critical information regarding clinical applications in risk assessment, disease prevention, diagnosis, and personalized therapeutics for areca nut-induced oral malignancy.
口腔癌是全球最常见的恶性疾病之一，槟榔是东南亚地区导致这种癌症的主要致癌物。已有广泛报道称，槟榔会在口腔细胞中引发多种细胞毒性作用，包括活性氧生成、炎症、组织缺氧、DNA损伤和细胞侵袭。最近，通过慢性暴露模型，发现了槟榔导致的更广泛的病理效应。这些效应包括自噬的诱导、上皮-间质转化的促进以及癌症干性转化的加速。临床研究结果支持了这些不良反应。口腔黏膜下纤维化是一种癌前病变，在有咀嚼槟榔习惯的地区很普遍。同样，有咀嚼槟榔习惯的口腔癌患者表现出更具侵袭性的表型，包括对放化疗的抵抗。在这篇综述中，我们全面讨论并简要总结了槟榔促成恶性转化的最新分子和细胞机制。这篇综述可能会为槟榔所致口腔恶性肿瘤的风险评估、疾病预防、诊断和个性化治疗等临床应用提供关键信息。
