ReferenceID 3853
Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells
J Hematol Oncol
BACKGROUND: The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for
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Record Fields
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- Reference Id
- 3853
- Evidence Id
- 20443
- Core Evidence Id
- 20443
- Source Reference Id
- 986
- Herb2 Reference Id
- HBREF001697
- Subject Paper Key
- HBIN007991_27658462
- Pubmed Id
- 27658462
- Doi
- 10.1186/s13045-016-0327-5
- Paper Title
- Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells
- Paper Abstract
- BACKGROUND: The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. METHODS: The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. RESULTS: The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C), alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. CONCLUSIONS: Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.
- Journal
- J Hematol Oncol
- Publish Year
- 2016
- Experiment Subject
- leukemia stem and progenitor cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Acute Myeloid Leukemia
- Paper Title Cn
- Paper Title En
- Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells
- Bilingual Status
- semi_complete