title: Withaferin A activates stress signalling proteins in high risk acute lymphoblastic leukemia.
abstract: Withaferin A, the principal bio-active component isolated from the Withaniasomnifera, has shown promising anti-leukemic activity in addition to anti-invasive and anti-metastatic activity. The present study demonstrates the effect of withaferin A on the cell cycle status and the phosphorylation/activation of proteins involved in signal transduction in t(4;11) and non-t(4;11) acute lymphoblastic leukemia (ALL) cell lines after treatment with withaferin A. The cells after treatment with the vehicle or 25 μM withaferin A for 1, 2, 4 and 8 h were examined using flow cytometric analysis. The results revealed that withaferin A treatment induced cell growth arrest at the S to G2/M phase transition of the cell cycle. Withaferin A treatment also induced the phosphorylation of stress signalling proteins, including the p38 mitogen-activated protein kinase, the c-Jun N-terminal kinase, c-Jun, the heat shock protein 27 and protein kinase B within 0 to 16 h. These results were observed using multiplex technology and Western blotting analysis. Thus withaferin A induces stress response leading to cell death. Therefore, withaferin A can be a potent therapeutic agent for the treatment of high risk ALL with chromosomal translocation t(4;11).
authors.affiliation: Key Laboratory of Paediatric Blood Diseases, Children's Hospital of Zhengzhou Zhengzhou 450053, China.
authors.forename: Li-Huan
authors.initials: LH
authors.lastname: Shi
authors.affiliation: Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University Guiyang 550004, China.
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Key Laboratory of Paediatric Blood Diseases, Children's Hospital of Zhengzhou Zhengzhou 450053, China.
authors.forename: Jun-Shan
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Science and Technology, Children's Hospital of Zhengzhou Zhengzhou 450053, China.
authors.forename: Yin-Bo
authors.initials: YB
authors.lastname: Gao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012307:Risk Factors; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological / Q000187:drug effects*; D013997:Time Factors; D014178:Translocation, Genetic; D054358:Withanolides / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D016755:Proto-Oncogene Proteins c-jun; D054358:Withanolides; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C009684:withaferin A
keywords: Withaniasomnifera; antileukemic activity; cell death; signal transduction; translocation