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

被引：21
|
作者：
Way, Tzong-Der [1 ,3 ]
Tsai, Shang-Jie [2 ]
Wang, Chao-Min [2 ]
Jhan, Yun-Lian [2 ]
Ho, Chi-Tang [4 ]
Chou, Chang-Hung [1 ,2 ,5 ]
机构：
[1] China Med Univ, Coll Biopharmaceut & Food Sci, Dept Biol Sci & Technol, Taichung 40402, Taiwan
[2] China Med Univ, Res Ctr Biodivers, Taichung 40402, Taiwan
[3] Asia Univ, Coll Hlth Sci, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan
[4] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08903 USA
[5] Natl Cheng Kung Univ, Dept Life Sci, Tainan 701, Taiwan
来源：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2015年 / 63卷 / 48期
关键词：
Rhododendron formosanum; non-small-cell lung carcinoma; cinnamtannin D1; Akt/mTOR; ERK1/2; A-TYPE PROANTHOCYANIDINS; CANCER-CELLS; SIGNALING PATHWAYS; APOPTOSIS; MACROAUTOPHAGY; FLAVONOIDS; INDUCTION; MECHANISM; THERAPY; GROWTH;
D O I：
10.1021/acs.jafc.5b04375
中图分类号：
S [农业科学];
学科分类号：
09 ;
摘要：
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 +/- 3.11% for 175 CNT D1 vs 69.28 +/- 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 ldnases 1/2 (ERK1/2) pathway, resulting in induction of autophagy.
引用
收藏
页码：10407 / 10417
页数：11
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