DT-13, a saponin monomer of dwarf lilyturf tuber, induces autophagy and potentiates anti-cancer effect of nutrient deprivation

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• 作者：Hongyang Li^a ; ¹ ; Li Sun^b ; ¹ ; Evandro Lopes de Carvalho^a ; ¹ ; Xinxin Li^c ; Xiaodan Lv^a ; Ghulam Jilany Khan^b ; Herve Semukunzi^a ; Shengtao Yuan^a ; ^{cpuYuanst@163.com" class="auth_mail" title="E-mail the corresponding author} ; Sensen Lin^b ; ^{chaphalss@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DT-13 (PubChem CID ; 101514160) ; Bafilomycin A1 (PubChem CID ; 6436223) ; Chloroquine (PubChem CID ; 2719)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：781
• 期：Complete
• 页码：164-172
• 全文大小：4472 K

文摘

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.