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

作　　者：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 YANG Min GUO De-An LIU Xuan 

机构地区：[1]Shanghai Institute of Materia Medica,Chinese Academy of Sciences

出　　处：《Chinese Journal of Natural Medicines》2016年第11期856-864,共9页中国天然药物（英文版）

基　　金：supported by the National Nature Science Foundation of China(No.81373964);Shanghai Science&Technology Support Program(No.13431900401);Shanghai Science&Technology Innovation Action Program(No.15140904800);the National Science&Technology Major Project of China(No.2014 ZX09301-306-03)

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 2α(p-eIF2α), C/EBP-homologous protein(CHOP), inositol-requiring enzyme 1α(IRE1α), and phosphorylated c-Jun NH_2-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.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 anderlying 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 zells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction zhromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G~ 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 2a （p-eIF2a）, C/EBP-homologous protein （CHOP）, inositol-requiring enzyme l a （IREla）, 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 zells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.

关 键 词：AGGLUTININ Arisaema heterophyllum Blume Human non-small-cell lung cancer A549 cell line APOPTOSIS AUTOPHAGY 

分 类 号：R965[医药卫生—药理学]