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Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells.
- Source :
-
Oncotarget [Oncotarget] 2016 Oct 04; Vol. 7 (40), pp. 65012-65023. - Publication Year :
- 2016
-
Abstract
- Leukemic stem cells (LSCs) greatly contribute to the initiation, relapse, and multidrug resistance of leukemia. Current therapies targeting the cell cycle and rapidly growing leukemic cells, including conventional chemotherapy, have little effect due to the self-renewal and differentiated malignant cells replenishment ability of LSCs despite their scarce supply in the bone marrow. Micheliolide (MCL) is a natural guaianolide sesquiterpene lactone (GSL) which was discovered in michelia compressa and michelia champaca plants, and has been shown to exert selective cytotoxic effects on CD34+CD38- LSCs. In this study, we demonstrate that DMAMCL significantly prolongs the lifespan of a mouse model of human acute myelogenous leukemia (AML). Mechanistic investigations further revealed that MCL exerted its cytotoxic effects via inhibition of NF-κB expression and activity, and by generating intracellular reactive oxygen species (ROS). These results provide valuable insight into the mechanisms underlying MCL-induced cytotoxicity of LSCs, and support further preclinical investigations of MCL-related therapies for the treatment of AML.
- Subjects :
- Animals
Apoptosis
Cell Self Renewal drug effects
Disease Models, Animal
Humans
Magnoliaceae immunology
Mice
Mice, SCID
NF-kappa B metabolism
Neoplastic Stem Cells drug effects
Reactive Oxygen Species metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Leukemia, Myeloid, Acute drug therapy
Neoplastic Stem Cells physiology
Sesquiterpenes, Guaiane pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 40
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27542251
- Full Text :
- https://doi.org/10.18632/oncotarget.11342