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Eur J Pharmacol ; 781: 164-72, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-27079642

ABSTRACT

Metabolic stress induces autophagy as a protective mechanism in tumorigenesis and development. Conversely, excessive autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, inhibited tumor metastasis and angiogenesis in previous studies. However, there is scarcity of data regarding the effect of DT-13 on autophagy process. Here, we demonstrated that DT-13 induced autophagy in human cancer cell lines and caused significant cell apoptosis under nutrient starvation. We firstly showed that DT-13 increased the accumulation of GFP-LC3 puncta and induced the expression of LC3-II in a dose- and time-dependent manner. DT-13 also upregulated the expression of Beclin-1, Atg-3 and Atg-7, and induced autophagic flux in human gastric cancer BGC-823 cells. We next found that low-toxic concentrations of DT-13 significantly induced apoptosis under nutrient deprivation. We finally demonstrated that the PI3K/Akt/mTOR signal pathway was involved in the cytotoxic effect of DT-13. Our data indicated that DT-13 was a novel autophagy inducer and might be considered in future treatment of cancer.


Subject(s)
Autophagy/drug effects , Liriope Plant/chemistry , Saponins/pharmacology , Apoptosis/drug effects , Autophagosomes/drug effects , Autophagosomes/metabolism , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Microtubule-Associated Proteins/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Saponins/chemistry , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Time Factors , Up-Regulation/drug effects , Vacuoles/drug effects , Vacuoles/metabolism
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