Arecoline and the 30-100 kDa fraction of areca nut extract differentially regulate mTOR and respectively induce apoptosis and autophagy: A pilot study

Shyun Yeu Liu, Mei Huei Lin, Yu Rung Hsu, Ya Yun Shih, Wei Fan Chiang, Chin Hai Lee, Ta Hsiung Chou, Young Chau Liu

研究成果: 雜誌貢獻文章

14 引文 斯高帕斯(Scopus)

摘要

Areca nut (AN) is recognized as a human carcinogen; however, few studies of the cytotoxic effects of AN ingredients on cells have been reported. In Taiwan, AN, lime and inflorescence of Piper betle are the common components of betel quid (BQ). We recently noticed that extract of AN (ANE), but not those of lime and inflorescence of Piper betle, induces rounding cell morphology and nuclear shrinkage in different types of carcinoma cells. In this study, the rounding cell activity was first traced to the partially purified ≥10 kDa fraction (ANE ≥ 10 K) and subsequently to the 30-100 kDa fraction (ANE 30-100 K). ANE and ANE ≥10 K stimulated nuclear shrinkage (P <0.001 in both cases) and the clearance of the cytoplasm. ANE, ANE ≥ 10 K, and ANE 30-100 K induced the cleavage of LC3-I (P <0.05, 0.01, and 0.05, respectively) and the emergence of autophagic vacuoles (AVs) and acidic vesicles. On the other hand, arecoline (Are, the major alkaloid of AN) triggered caspase-3 activation, peri-nuclear chromatin condensation, and micronucleation. Meanwhile, ANE 30-100 K, but not Are, inhibited the phosphorylation of the mammalian target of rapamycin (mTOR)-Ser2448. In conclusion, this study demonstrates that different AN ingredients exerting differential impact on mTOR-Ser2448 phosphorylation are capable of triggering apoptosis and autophagy.
原文英語
頁(從 - 到)823-831
頁數9
期刊Journal of Biomedical Science
15
發行號6
DOIs
出版狀態已發佈 - 十一月 2008

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

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