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DT-13, a saponin monomer of dwarf lilyturf tuber, induces autophagy and potentiates anti-cancer effect of nutrient deprivation.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2016 Jun 15; Vol. 781, pp. 164-72. Date of Electronic Publication: 2016 Apr 12. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- 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
Autophagy drug effects
Liriope Plant chemistry
Saponins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 781
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27079642
- Full Text :
- https://doi.org/10.1016/j.ejphar.2016.04.016