Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress

doi:10.1016/S1875-5364(16)30102-9

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	Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress
	Feng Li-Xing; Sun Peng; Mi Tian; Liu Miao; Liu Wang; Yao Si; Cao Yi-Min; Yu Xiao-Lu; Wu Wan-Ying; Jiang Bao-Hong
刊名	CHINESE JOURNAL OF NATURAL MEDICINES
	2016-11
卷号	14 期号:11 页码:856-864
关键词	Agglutinin Arisaema heterophyllum Blume Human non-small-cell lung cancer A549 cell line Apoptosis Autophagy
ISSN号	2095-6975
DOI	10.1016/S1875-5364(16)30102-9
文献子类	Article
英文摘要	Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume (AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G(1) phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2 alpha), C/EBP-homologous protein (CHOP), inositol-requiring enzyme 1 alpha (IRE1 alpha), and phosphorylated c-Jun NH2-terminal kinase (p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles (AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.
资助项目	National Nature Science Foundation of China[81373964] ; Shanghai Science & Technology Support Program[13431900401] ; Shanghai Science & Technology Innovation Action Program[15140904800] ; National Science & Technology Major Project of China[2014 ZX09301-306-03]
WOS关键词	ENDOPLASMIC-RETICULUM STRESS ; CANCER-CELLS ; CONCANAVALIN-A ; RHIZOMA-ARISAEMATIS ; THERAPEUTIC TARGET ; MEDIATED APOPTOSIS ; HEPATOMA-CELLS ; PLANT-LECTINS ; BREAST-CANCER ; IN-VITRO
WOS研究方向	Integrative & Complementary Medicine ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5864419
出版者	CHINESE JOURNAL NATURAL MEDICINES
WOS记录号	WOS:000390587500006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275826]
专题	上海中药现代化研究中心
通讯作者	Guo De-An; Liu Xuan
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Feng Li-Xing,Sun Peng,Mi Tian,et al. Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress[J]. CHINESE JOURNAL OF NATURAL MEDICINES,2016,14(11):856-864.
APA	Feng Li-Xing.,Sun Peng.,Mi Tian.,Liu Miao.,Liu Wang.,...&Liu Xuan.(2016).Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress.CHINESE JOURNAL OF NATURAL MEDICINES,14(11),856-864.
MLA	Feng Li-Xing,et al."Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress".CHINESE JOURNAL OF NATURAL MEDICINES 14.11(2016):856-864.