Impacts of autophagy-inducing ingredient of areca nut on tumor cells

Ching Yu Yen, Wei Fan Chiang, Shyun Yeu Liu, Chung Chih Lin, Kuo An Liao, Che Yi Lin, Wan Fang Hsieh, Yon Chi Cheng, Kai Cheng Hsu, Pin Yen Lin, Tai Chi Chen, I. Ling Lee, Mei Huei Lin, Young Chau Liu

研究成果: 雜誌貢獻文章

5 引文 (Scopus)

摘要

Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from longterm non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions.
原文英語
文章編號e0128011
期刊PLoS One
10
發行號5
DOIs
出版狀態已發佈 - 五月 1 2015

指紋

Areca
Nuts
autophagy
Autophagy
AMP-Activated Protein Kinases
Tumors
ingredients
Cells
T-cells
Mitogen-Activated Protein Kinase Kinases
AMP-activated protein kinase
Neoplasms
Phosphotransferases
extracts
Cell death
tongue
Tongue
Caspase 3
Carcinogens
Small Interfering RNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

引用此文

Yen, C. Y., Chiang, W. F., Liu, S. Y., Lin, C. C., Liao, K. A., Lin, C. Y., ... Liu, Y. C. (2015). Impacts of autophagy-inducing ingredient of areca nut on tumor cells. PLoS One, 10(5), [e0128011]. https://doi.org/10.1371/journal.pone.0128011

Impacts of autophagy-inducing ingredient of areca nut on tumor cells. / Yen, Ching Yu; Chiang, Wei Fan; Liu, Shyun Yeu; Lin, Chung Chih; Liao, Kuo An; Lin, Che Yi; Hsieh, Wan Fang; Cheng, Yon Chi; Hsu, Kai Cheng; Lin, Pin Yen; Chen, Tai Chi; Lee, I. Ling; Lin, Mei Huei; Liu, Young Chau.

於: PLoS One, 卷 10, 編號 5, e0128011, 01.05.2015.

研究成果: 雜誌貢獻文章

Yen, CY, Chiang, WF, Liu, SY, Lin, CC, Liao, KA, Lin, CY, Hsieh, WF, Cheng, YC, Hsu, KC, Lin, PY, Chen, TC, Lee, IL, Lin, MH & Liu, YC 2015, 'Impacts of autophagy-inducing ingredient of areca nut on tumor cells', PLoS One, 卷 10, 編號 5, e0128011. https://doi.org/10.1371/journal.pone.0128011
Yen, Ching Yu ; Chiang, Wei Fan ; Liu, Shyun Yeu ; Lin, Chung Chih ; Liao, Kuo An ; Lin, Che Yi ; Hsieh, Wan Fang ; Cheng, Yon Chi ; Hsu, Kai Cheng ; Lin, Pin Yen ; Chen, Tai Chi ; Lee, I. Ling ; Lin, Mei Huei ; Liu, Young Chau. / Impacts of autophagy-inducing ingredient of areca nut on tumor cells. 於: PLoS One. 2015 ; 卷 10, 編號 5.
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abstract = "Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from longterm non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions.",
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AU - Yen, Ching Yu

AU - Chiang, Wei Fan

AU - Liu, Shyun Yeu

AU - Lin, Chung Chih

AU - Liao, Kuo An

AU - Lin, Che Yi

AU - Hsieh, Wan Fang

AU - Cheng, Yon Chi

AU - Hsu, Kai Cheng

AU - Lin, Pin Yen

AU - Chen, Tai Chi

AU - Lee, I. Ling

AU - Lin, Mei Huei

AU - Liu, Young Chau

PY - 2015/5/1

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