title: Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8;21) Leukemia.
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.
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China. xjyu_hbmu@126.com.|Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. xjyu_hbmu@126.com.|Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China. xjyu_hbmu@126.com.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China. ruanxuzhi@163.com.
authors.forename: Xuzhi
authors.initials: X
authors.lastname: Ruan
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China. zhangjx@hbmu.edu.cn.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. zhaoqun@sibs.ac.cn.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000096:biosynthesis*; D014178:Translocation, Genetic; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050676:Core Binding Factor Alpha 2 Subunit; D053978:Pentacyclic Triterpenes; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors; D014315:Triterpenes; D019009:Proto-Oncogene Proteins c-kit; C050414:celastrol
keywords: 21) leukemia; C-KIT; apoptosis; celastrol; mitochondrial dysfunction; t(8