Journal
JOURNAL OF CANCER
Volume 10, Issue 17, Pages 4054-4062Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.29765
Keywords
areca nut; oral cancer; oral submucosal fibrosis; reactive oxygen species; tissue hypoxia; cell invasion; epithelial-mesenchymal transition; cancer stemness
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Funding
- Chang Gung Medical Foundation [CMRPD1G0451~3, CMRPG3G1411~3]
- Ministry of Science and Technology of Taiwan [MOST 106-2320-B-182-025-MY3]
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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.
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