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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)823-831
Number of pages9
JournalJournal of Biomedical Science
Volume15
Issue number6
DOIs
Publication statusPublished - Nov 2008

Fingerprint

Arecoline
Areca
Nuts
Autophagy
Sirolimus
Apoptosis
Piper betle
Inflorescence
Phosphorylation
Vacuoles
Taiwan
Alkaloids
Caspase 3
Carcinogens
Chromatin
Condensation
Cytoplasm
Chemical activation
Cells
Carcinoma

Keywords

  • Apoptosis
  • Areca nut
  • Arecoline
  • Autophagy
  • Mammalian target of rapamycin (mTOR)

ASJC Scopus subject areas

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

Cite this

Arecoline and the 30-100 kDa fraction of areca nut extract differentially regulate mTOR and respectively induce apoptosis and autophagy : A pilot study. / Liu, Shyun Yeu; Lin, Mei Huei; Hsu, Yu Rung; Shih, Ya Yun; Chiang, Wei Fan; Lee, Chin Hai; Chou, Ta Hsiung; Liu, Young Chau.

In: Journal of Biomedical Science, Vol. 15, No. 6, 11.2008, p. 823-831.

Research output: Contribution to journalArticle

Liu, Shyun Yeu ; Lin, Mei Huei ; Hsu, Yu Rung ; Shih, Ya Yun ; Chiang, Wei Fan ; Lee, Chin Hai ; Chou, Ta Hsiung ; Liu, Young Chau. / Arecoline and the 30-100 kDa fraction of areca nut extract differentially regulate mTOR and respectively induce apoptosis and autophagy : A pilot study. In: Journal of Biomedical Science. 2008 ; Vol. 15, No. 6. pp. 823-831.
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T1 - Arecoline and the 30-100 kDa fraction of areca nut extract differentially regulate mTOR and respectively induce apoptosis and autophagy

T2 - A pilot study

AU - Liu, Shyun Yeu

AU - Lin, Mei Huei

AU - Hsu, Yu Rung

AU - Shih, Ya Yun

AU - Chiang, Wei Fan

AU - Lee, Chin Hai

AU - Chou, Ta Hsiung

AU - Liu, Young Chau

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N2 - 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.

AB - 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.

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