Long-term stimulation of areca nut components results in increased chemoresistance through elevated autophagic activity

Ching Yu Yen, Wei Fan Chiang, Shyun Yeu Liu, Pse Chou Cheng, Sheng Yang Lee, Wen Zhai Hong, Pin Yen Lin, Mei Huei Lin, Young Chau Liu

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)


Background: We previously demonstrated the autophagy-inducing activity in the crude extract of areca nut (ANE) and its 30-100 kDa fraction (ANE 30-100 K). This study aimed to analyze whether chronic ANE and ANE 30-100 K stimulations lead to higher stress resistance and autophagic activity in oral cells, and whether the resulting autophagic status in stimulated cells correlates with stress resistance. Materials and Methods: Malignant cells from the mouth oral epidermoid carcinoma Meng-1 (OECM-1) and blood (Jurkat T) origins were stimulated with non-cytotoxic ANE and ANE 30-100 K for 3 months. Sensitivity to anticancer drugs of and autophagy status in stimulated cells, analyzed respectively by XTT assay and calculating microtubule-associated protein 1 light chain 3-II LC3-II/β-actin ratios from Western blot, were compared to non-treated cells. Autophagy inhibitors, 3-methyladenine (3-MA) and chloroquine (CQ), were used to assess whether autophagy inhibition interferes the altered chemoresistance. Results: Areca nut extract-stimulated (ANE-s) and ANE 30-100 K-stimulated (30-100 K-s) OECM-1 and Jurkat T cells generally exhibited higher cisplatin and 5-fluorouracil (5-FU) resistances, compared to non-stimulated cells. Most stimulated cells expressed significantly higher levels of LC3-II and Atg4B proteins. Interestingly, these cells also showed stronger tolerances against hypoxia environment and expressed higher LC3-II levels under glucose-deprived and hypoxia conditions. Finally, both 3-MA and CQ alleviated, albeit to different degrees, the increased chemoresistance in ANE-s and/or 30-100 K-s cells. Conclusions: Chronic stimulations of ANE or ANE 30-100 K may increase tolerance of oral cancer and leukemia T cells to anticancer drugs, as well as to glucose deprivation and hypoxia conditions, and cause an elevation of autophagy activity responsible for increased drug resistance.
頁(從 - 到)91-96
期刊Journal of Oral Pathology and Medicine
出版狀態已發佈 - 2月 2014

ASJC Scopus subject areas

  • 癌症研究
  • 病理學與法醫學
  • 耳鼻咽喉科
  • 口腔外科
  • 牙周病
  • 一般醫學


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