2012 Fiscal Year Final Research Report
Research on natural products with autophagy-dependent anti-tumoractivity
| Project/Area Number |
21590023
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Yukiko 東京薬科大学, 薬学部, 助手 (70434016)
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| Project Period (FY) |
2009 – 2012
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| Keywords | 抗腫瘍活性 / 細胞毒性 / オートファジー / アポトーシス / Lycoris albiflora / アルカロイド / リコリシジノール / Larrea tridentata / Santalum album / Fritillaria meleagris / Adonis aestivalis / アルカロイド / リグナン / テルペノイド / ステロイド |
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| Research Abstract |
To discover natural products with autophagy-dependent anti-tumor activity, cytotoxicity-guided fractionations were carried out with the methanolic extracts of Lycoris albiflorabulbs, Larrea tridentataaerial parts, Santalum albumheartwood, Fritillaria meleagrisbulbs and Adonis aestivalis seeds. As a result, lycoricidinol, a phenanthridine-type alkaloid, which potently induced apoptotic cell death in both HL-60 human promyelocytic leukemia cells and HSC-2 human oral squamous cell carcinoma cells with IC50values of 0.018 mM and 0.053 mM, respectively, was isolated from L. albiflorabulbs. Lycoricidinol induced transient autophagy at the early stage of the apoptotic cell death process in HSC-2 cells. An autophagy inhibitor decreased the potent apoptosis-inducible activity of lycoricidinol, which suggests that the transient autophagic induction is associated with the strong apoptotic cell death of HSC-2 cells by lycoricidinol. Several secondary metabolites isolated from H. brachyandrus, L. tridentate, S. album, F. meleagris and A. aestivalis exhibited apoptosis-inducible activity in cultured tumor cells, but did not induce autophagy
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