Impacts of Autophagy-Inducing Ingredient of Areca Nut on Tumor Cells

doi:10.1371/journal.pone.0128011

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Title:	Impacts of Autophagy-Inducing Ingredient of Areca Nut on Tumor Cells
Authors:	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
Contributors:	生物科技系
Keywords:	Activated protein-kinase Beclin1-independent autophagy Ampk signaling pathway 30-100 kda fraction Cancer-cells Cross-talk Induction Apoptosis Macroautophagy aAecoline
Date:	2015-05
Issue Date:	2016-04-19 19:06:31 (UTC+8)
Publisher:	Public Library Science
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 long-term 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.
Relation:	Plos One, v.10 n.5, Article ID e0128011
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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