title: DT-13, a saponin monomer of dwarf lilyturf tuber, induces autophagy and potentiates anti-cancer effect of nutrient deprivation.
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.
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Evandro Lopes
authors.initials: EL
authors.lastname: de Carvalho
authors.affiliation: Tianjin Tasly Holding Group Co. Ltd., Pujihe East Road, BeiChen District, Tianjin 300410, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Lv
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ghulam Jilany
authors.initials: GJ
authors.lastname: Khan
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Herve
authors.initials: H
authors.lastname: Semukunzi
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpuYuanst@163.com.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China. Electronic address: chaphalss@126.com.
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D031424:Liriope Plant / Q000737:chemistry*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012503:Saponins; D058570:TOR Serine-Threonine Kinases; C477012:MAP1LC3A protein, human; C578958:ruscogenin-1-O-(glucopyranosyl-(1-2))(xylopyranosyl-(1-3))fucopyranoside
keywords: Apoptosis; Autophagy; Bafilomycin A1 (PubChem CID: 6436223); Chloroquine (PubChem CID: 2719); DT-13; DT-13 (PubChem CID: 101514160); Nutrient deprivation; mTOR