withanolides and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

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).

Topics: Antineoplastic Agents, Phytogenic; Cell Death; Cell Line, Tumor; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 4; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; JNK Mitogen-Activated Protein Kinases; Molecular Chaperones; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-jun; Risk Factors; S Phase Cell Cycle Checkpoints; Signal Transduction; Stress, Physiological; Time Factors; Translocation, Genetic; Withanolides