Poster Presentation 38th Lorne Cancer Conference 2026

Regulation of AKR1Cs’ expression of SAS oral cancer cells by areca nut and arecoline (#167)

Jiiang-Huei Jeng 1 2 3 4 , Wen-Hui Chen 5
  1. National Taiwan University College of Medicine, Chung-Cheng District, TAIPEI, Taiwan
  2. Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
  3. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  4. Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  5. Department of Dentistry, E-Da General Hospital, Kaohsiung, Taiwan

Oral cancer is popular in Taiwan, India, Papua New Guinea and Asian-Pacific Islands, possibly due to oral habits such as betel quid (BQ) chewing, Tobacco and alcohol consumption. Areca nut (AN) as a main BQ component, and arecoline (an areca alkaloid), are considered as the major carcinogenic factors. However, the pathogenic mechanisms of oral cancer in BQ chewers are not clear. Aldo-keto reductases (AKRs) C family members (AKR1C1-AKR1C4) catalyze NADPH-dependent reductions, and AKR1Cs’ expression is associated with malignant transformation and cancer resistance. However, their expression in oral epithelial cells and roles in AN- and arecoline-induced events such as prostaglandin E2 (PGE2) and matrix metalloproteinase-9 (MMP-9) production are not understood. In this study, SAS oral cancer cells were exposed to AN extract (ANE) or arecoline for 24 hours. Cellular AKR1Cs’ mRNA and protein expression was analyzed by real-time PCR and western blotting, respectively. SAS cells were pretreated with AKR1C inhibitors (AKR1C-IN), and then exposed to ANE. Cell viability was estimated by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PGE2 and MMP-9 production were measured by ELISA. We found that ANE stimulated AKR1C1, AKR1C2, AKR1C3 and AKR1C4 mRNA and protein expression of SAS cells. Arecoline also induced AKR1C1-AKR1C4 expression of SAS cells. ANE stimulated PGE2 and MMP-9 production in SAS cells. Moreover, blocking of AKR1Cs by AKR1C inhibitor (AKR1C-IN) attenuated the ANE-induced PGE2 but not MMP-9 production and changes in cell viability. These results indicate that AN can stimulate tissue inflammatory and matrix destruction, and contribute to oral carcinogenesis. ANE and arecoline stimulate AKR1C1-AKR1C4 of oral epithelial cells to mediate PGE2 production. Since AKR1Cs are crucial for cancer development and resistance, regulation of AKR1Cs by ANE and arecoline implied the involvement of AN components in oral carcinogenesis. Future use of AKR1C inhibitors for prevention/treatment of oral cancers awaits investigation.