6-Shogaol, an Active Constituent of Dietary Ginger, Induces Autophagy by Inhibiting the AKT/mTOR Pathway in Human Non-Small Cell Lung Cancer A549 Cells

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• 作者：Jen-Yu Hung ; Ya-Ling Hsu ; Chien-Te Li ; Ying-Chin Ko ; Wen-Chiu Ni ; Ming-Shyan Huang ; Po-Lin Kuo
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2009
• 出版时间：October 28, 2009
• 年：2009
• 卷：57
• 期：20
• 页码：9809-9816
• 全文大小：913K
• 年卷期：v.57,no.20(October 28, 2009)
• ISSN：1520-5118

文摘

This study is the first study to investigate the anticancer effect of 6-shogaol in human non-small cell lung cancer A549 cells. 6-Shogaol inhibited cell proliferation by inducing autophagic cell death, but not, predominantly, apoptosis. Pretreatment of cells with 3-methyladenine (3-MA), an autophagy inhibitor, suppressed 6-shogaol mediated antiproliferation activity, suggesting that induction of autophagy by 6-shogaol is conducive to cell death. We also found that 6-shogaol inhibited survival signaling through the AKT/mTOR signaling pathway by blocking the activation of AKT and downstream targets, including the mammalian target of rapamycin (mTOR), forkhead transcription factors (FKHR) and glycogen synthase kinase-3β (GSK-3β). Phosphorylation of both of mTOR’s downstream targets, p70 ribosomal protein S6 kinase (p70S6 kinase) and 4E-BP1, was also diminished. Overexpression of AKT by AKT cDNA transfection decreased 6-shogaol mediated autophagic cell death, supporting inhibition of AKT beneficial to autophagy. Moreover, reduction of AKT expression by siRNA potentiated 6-shogaol’s effect, also supporting inhibition of AKT beneficial to autophagy. Taken together, these findings suggest that 6-shogaol may be a promising chemopreventive agent against human non-small cell lung cancer.