AGS 인체 위암 세포에서 Akt/mTOR/GSK-3β 신호경로 조절을 통한 개똥쑥 추출물의 Apoptosis 유도 효과 (Apoptosis-Induced Effects of Extract from Artemisia annua Linné by Modulating Akt/mTOR/GSK-3β Signal Pathway in AGS Human Gastric Carcinoma Cells)

서지정보

· 발행기관 : 한국식품영양과학회
· 수록지 정보 : 한국식품영양과학회지 / 45권 / 9호 / 1257 ~ 1264페이지
· 저자명 : 김은지, 김근태, 김보민, 임은경, 김상용, 김영민

초록

Extracts from Artemisia annua Linné (AAE) have various functions (anti-malaria, anti-virus, and anti-oxidant). However, the mechanism of the effects of AAE is not well known. Thus, we determined the apoptotic effects of AAE in AGS human gastric carcinoma cells. In this study, we suggested that AAE may exert cancer cell apoptosis through the Akt/mammalian target of rapamycin (mTOR)/glycogen synthase kinase (GSK)-3β signal pathway and mitochondria-mediated apoptotic proteins. Activation by Akt phosphorylation resulted in cell proliferation through phosphorylation of tuberous sclerosis complex 2 (TSC2), mTOR, and GSK-3β. Thus, de-phosphorylation of Akt inhibited cell proliferation and induced apoptosis through inhibition of Akt, mTOR, phosphorylation of GSK-3β at serine9, and control of Bcl-2 family members. Inhibition of GSK-3β attenuated loss of mitochondrial membrane potential and release of cytochrome C. Bax and pro-apoptotic proteins were activated by their translocation into mitochondria from the cytosol. Translocation of Bax induced outer membrane transmission and generated apoptosis through cytochrome C release and caspase activity. We also measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase assay, Hoechst 33342 staining, AnnexinⅤ-PI staining, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl- imidacarbocyanine iodide staining, and Western blotting. Accordingly, our study showed that AAE treatment to AGS cells resulted in inhibition of Akt, TSC2, GSK-3β-phosphorylated, Bim, Bcl-2, and pro-caspase 3 as well as activation of Bax and Bak expression. These results indicate that AAE induced apoptosis via a mitochondrial event through regulation of the Akt/mTOR/GSK-3β signaling pathways.

영어초록

Extracts from Artemisia annua Linné (AAE) have various functions (anti-malaria, anti-virus, and anti-oxidant). However, the mechanism of the effects of AAE is not well known. Thus, we determined the apoptotic effects of AAE in AGS human gastric carcinoma cells. In this study, we suggested that AAE may exert cancer cell apoptosis through the Akt/mammalian target of rapamycin (mTOR)/glycogen synthase kinase (GSK)-3β signal pathway and mitochondria-mediated apoptotic proteins. Activation by Akt phosphorylation resulted in cell proliferation through phosphorylation of tuberous sclerosis complex 2 (TSC2), mTOR, and GSK-3β. Thus, de-phosphorylation of Akt inhibited cell proliferation and induced apoptosis through inhibition of Akt, mTOR, phosphorylation of GSK-3β at serine9, and control of Bcl-2 family members. Inhibition of GSK-3β attenuated loss of mitochondrial membrane potential and release of cytochrome C. Bax and pro-apoptotic proteins were activated by their translocation into mitochondria from the cytosol. Translocation of Bax induced outer membrane transmission and generated apoptosis through cytochrome C release and caspase activity. We also measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase assay, Hoechst 33342 staining, AnnexinⅤ-PI staining, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl- imidacarbocyanine iodide staining, and Western blotting. Accordingly, our study showed that AAE treatment to AGS cells resulted in inhibition of Akt, TSC2, GSK-3β-phosphorylated, Bim, Bcl-2, and pro-caspase 3 as well as activation of Bax and Bak expression. These results indicate that AAE induced apoptosis via a mitochondrial event through regulation of the Akt/mTOR/GSK-3β signaling pathways.

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