Int J Med Sci 2021; 18(15):3452-3462. doi:10.7150/ijms.61570 This issue

Research Paper

Areca nut extract (ANE) inhibits the progression of hepatocellular carcinoma cells via activation of ROS production and activation of autophagy

Po-Li Wei1,2,3,4, Chin-Sheng Hung2, Hsuan-Hsuan Lu5, Uyanga Batzorig2, Chien-Yu Huang2,6,7, Yu-Jia Chang8,9,10✉

1. Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
2. Department of Surgery, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
3. Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
4. Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
5. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
6. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
7. Division of Colon and Rectal, Department of Surgery, Shuang Ho Hospital, Taipei Medical University.
8. Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
9. Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
10. Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

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Citation:
Wei PL, Hung CS, Lu HH, Batzorig U, Huang CY, Chang YJ. Areca nut extract (ANE) inhibits the progression of hepatocellular carcinoma cells via activation of ROS production and activation of autophagy. Int J Med Sci 2021; 18(15):3452-3462. doi:10.7150/ijms.61570. Available from https://www.medsci.org/v18p3452.htm

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Abstract

Graphic abstract

Hepatocellular carcinoma (HCC) is a worldwide health problem. Currently, there is no effective therapeutic strategy for HCC patients. Chewing areca nut is closely associated with oral cancer and liver cirrhosis. The therapeutic effect of areca nut extract (ANE) on HCC is unknown. Our results revealed that ANE treatment caused a reduction in cell viability and an increase in cell apoptosis and suppressed tumor progression in xenograft models. ANE-treated didn't induce liver tumor in nude mice. For mechanism dissection, ANE treatment caused ROS-mediated autophagy and lysosome formation. Pretreatment with an ROS inhibitor, aminoguanidine hemisulfate (AGH), abolished ANE-induced ROS production. ANE treated cells caused an increase in light chain 3 (LC3)-I to -II conversion, anti-thymocyte globulin 5+12 (ATG5+12), and beclin levels, and apoptosis related-protein changes (an increases in BAX, cleaved poly(ADP-ribose) polymerase (c-PARP), and a decrease in the Bcl-2 level). In conclusion, our study demonstrated that the ANE may be a new potential compound for HCC therapy.

Keywords: hepatocellular carcinoma, ANE, apoptosis, ROS, autophagy, lysosome