Seong Yeong-Ae, Shin Pyung-Gyun, Yoon Jin-Soo, Yadunandam Anandam Kasin, Kim Gun-Do
Department of Microbiology, College of Natural Sciences, Pukyong National University, 45, Yongso-ro, Nam-Gu, Busan, 608-737, Korea.
Cell Biochem Biophys. 2014 Mar;68(2):369-77. doi: 10.1007/s12013-013-9717-2.
Anacardic acid (AA, 2-hydroxy-6-pentadecylbenzoic acid), a constituent of the cashew-nut shell, has a variety of beneficial effects on the treatment of cancer and tumors. However, the fact that AA induces ER stress and autophagy in cancer cell is not known. We investigated the effect of AA on ER-stress and autophagy-induced cell death in cancer cells. Because of our interest in lung cancer, we used the non-small cell lung adenocarcinoma A549 cells treated with 3.0 μg/ml of AA for this research. In this research we found that AA induces intracellular Ca(2+) mobilization and ER stress. AA induced the ER stress-inducing factors, especially IRE1α, and the hallmarks of UPR, Grp78/Bip and GADD153/CHOP. AA inhibited the expression of p-PERK and its downstream substrate, p-elF2α. We also demonstrated that AA induces autophagy. Up-regulation of autophagy-related genes and the appearance of autophagosome in transfected cells with green fluorescent protein (GFP)-LC3 and GFP-Beclin1 plasmids showed the induction of autophagy in AA-treated A549 cells. The morphological analysis of intracellular organelles by TEM also showed the evidence that AA induces ER stress and autophagy. For the first time, our research showed that AA induces ER stress and autophagy in cancer cells.
漆树酸（AA，2-羟基-6-十五烷基苯甲酸）是腰果壳的一种成分，对癌症和肿瘤的治疗具有多种有益作用。然而，AA是否能在癌细胞中诱导内质网应激（ER应激）和自噬尚不清楚。我们研究了AA对癌细胞中ER应激和自噬诱导的细胞死亡的影响。由于我们对肺癌感兴趣，因此在本研究中使用了用3.0μg/ml AA处理的非小细胞肺腺癌A549细胞。在本研究中，我们发现AA诱导细胞内Ca(2+)动员和ER应激。AA诱导了ER应激诱导因子，尤其是IRE1α，以及未折叠蛋白反应（UPR）的标志物Grp78/Bip和GADD153/CHOP。AA抑制了p-PERK及其下游底物p-elF2α的表达。我们还证明了AA诱导自噬。用绿色荧光蛋白（GFP）-LC3和GFP-Beclin1质粒转染的细胞中自噬相关基因的上调和自噬体的出现表明AA处理的A549细胞中自噬被诱导。通过透射电子显微镜（TEM）对细胞内细胞器的形态学分析也显示了AA诱导ER应激和自噬的证据。我们的研究首次表明AA能在癌细胞中诱导ER应激和自噬。
