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Article Publish Status: FREE
Abstract Title:

Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells.

Abstract Source:

J Hematol Oncol. 2016 Sep 22 ;9(1):93. Epub 2016 Sep 22. PMID: 27658462

Abstract Author(s):

Yahui Ding, Huier Gao, Yu Zhang, Ye Li, Neil Vasdev, Yingdai Gao, Yue Chen, Quan Zhang

Article Affiliation:

Yahui Ding

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.

Study Type : In Vitro Study

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Sayer Ji
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