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：22

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

页码：10407 / 10417

页数：11

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