Abstract
Resistance to chemotherapy is a major challenge to improving overall survival in Acute Myeloid Leukemia (AML). Therefore, the development of innovative therapies and the identification of more novel agents for AML are urgently needed. Celastrol, a compound extracted from the Chinese herb Tripterygium wilfordii Hook, exerts anticancer activity. We investigated the effect of celastrol in the t(8;21) AML cell lines Kasumi-1 and SKNO-1. We demonstrated that inhibition of cell proliferation activated caspases and disrupted mitochondrial function. In addition, we found that celastrol downregulated the AML1-ETO fusion protein, therefore downregulating C-KIT kinases and inhibiting AKT, STAT3 and Erk1/2. These findings provide clear evidence that celastrol might provide clinical benefits to patients with t(8;21) leukemia.
Keywords:
21) leukemia; C-KIT; apoptosis; celastrol; mitochondrial dysfunction; t(8.
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chromosomes, Human, Pair 21
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Chromosomes, Human, Pair 8
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Core Binding Factor Alpha 2 Subunit / biosynthesis*
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Down-Regulation / drug effects
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Humans
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Leukemia, Myeloid, Acute / drug therapy*
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / metabolism
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Pentacyclic Triterpenes
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Proto-Oncogene Proteins / biosynthesis*
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Proto-Oncogene Proteins c-kit / biosynthesis*
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RUNX1 Translocation Partner 1 Protein
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Transcription Factors / biosynthesis*
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Translocation, Genetic
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Triterpenes / therapeutic use*
Substances
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Antineoplastic Agents, Phytogenic
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Core Binding Factor Alpha 2 Subunit
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Pentacyclic Triterpenes
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Proto-Oncogene Proteins
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RUNX1 Translocation Partner 1 Protein
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RUNX1 protein, human
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RUNX1T1 protein, human
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Transcription Factors
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Triterpenes
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Proto-Oncogene Proteins c-kit
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celastrol