Cinnamtannin D1 from Rhododendron formosanum Induces Autophagy via the Inhibition of Akt/mTOR and Activation of ERK1/2 in Non-Small-Cell Lung Carcinoma Cells

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• 作者：Tzong-Der Way ; Shang-Jie Tsai ; Chao-Min Wang ; Yun-Lian Jhan ; Chi-Tang Ho ; Chang-Hung Chou
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2015
• 出版时间：December 9, 2015
• 年：2015
• 卷：63
• 期：48
• 页码：10407-10417
• 全文大小：657K
• ISSN：1520-5118

文摘

In our previous study, ursolic acid present in the leaves of Rhododendron formosanum was found to possess antineoplastic activity. We further isolated and unveiled a natural product, cinnamtannin D1 (CNT D1), an A-type procyanidin trimer in R. formosanum also exhibiting anticancer efficacy that induced G1 arrest (83.26 卤 3.11% for 175 渭M CNT D1 vs 69.28 卤 1.15% for control, p < 0.01) and autophagy in non-small-cell lung carcinoma (NSCLC) cells. We found that CNT D1-mediated autophagy was via the noncanonical pathway, being beclin-1-independent but Atg5 (autophagy-related genes 5)-dependent. Inhibition of autophagy with a specific inhibitor enhanced cell death, suggesting a cytoprotective function for autophagy in CNT D1-treated NSCLC cells. Moreover, CNT D1 inhibited the Akt/mammalian target of the rapamycin (mTOR) pathway and activated the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, resulting in induction of autophagy.