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.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY(2015)
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.
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关键词
Rhododendron formosanum,non-small-cell lung carcinoma,cinnamtannin D1,Akt/mTOR,ERK1/2
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