Autophagy induction by the 30-100 kDa fraction of areca nut in both normal and malignant cells through reactive oxygen species

Mei Huei Lin, Wan Fang Hsieh, Wei Fan Chiang, Wen Zhai Hong, Yu Rung Hsu, Yon Chi Cheng, Tai Chi Chen, Kai Cheng Hsu, Pin Yan Lina, Shyun Yeu Liu, Young Chau Liu

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Areca nut (AN) is an addictive carcinogen used by about 200-600 million people worldwide. Some AN components are shown to induce apoptosis; however, we previously demonstrated that AN extract (ANE) and the 30-100 kDa fraction of ANE (ANE 30-100K) induced autophagy-like responses, such as swollen cell morphology, empty cytoplasm, acidic vesicles, and LC3-II accumulation, in an oral cancer cell line, OECM-1. To further assess the responses of other cell types to ANE 30-100K, we used both normal and malignant cells as the targets of ANE 30-100K and found that normal oral fibroblasts (CMT415), peripheral blood lymphocytes (PBLs), Jurkat leukemia T cells, and esophageal carcinoma cells (CE81T/VGH) exhibited similar responses after ANE 30-100K challenge. ANE 30-100K drastically increased acidic vesicle-containing PBLs isolated from two independent donors (from 0.1% to 92.1% and 2.9% to 64.2%). Furthermore, both ANE- and ANE 30-100K-induced LC3-II accumulation in CMT415 and CE81T/VGH was further increased in the presence of the lysosomal protease inhibitors (pepstatin A, E64d, and leupeptin). On the other hand, ANE 30-100K also increased the level of intracellular reactive oxygen species (ROS), and the ROS scavengers, N-acetylcysteine (NAC) and Tiron, inhibited ANE 30-100K-induced cell death and LC3-II accumulation. Collectively, these results suggest the existence of an autophagy-inducing AN ingredient (AIAI) in ANE 30-100K, which renders ANE as an autophagic flux inducer through ROS in both normal and malignant cells.

Original languageEnglish
Pages (from-to)822-828
Number of pages7
JournalOral Oncology
Issue number11
Publication statusPublished - Nov 2010


  • ANE 30-100K
  • Apoptosis
  • Areca nut
  • Autophagy
  • Carcinoma
  • Fibroblast
  • Lymphocyte
  • Oral cancer
  • ROS

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research


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