Cucurbitacin B inhibits STAT3 and the Raf/MEK/ERK pathway in leukemia cell line K562

• Published in: Cancer letters Vol. 289; no. 1; pp. 46 - 52
• Main Authors: Chan, Kin Tak, Li, Kwan, Liu, Shiu Lam, Chu, Kee Hung, Toh, Melvin, Xie, Wei Dong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2010; Elsevier Limited
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Blotting, Western; Cancer; Cell culture; Cell cycle; Cell growth; Cucurbitaceae; Cucurbitacin B; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flow Cytometry; Hematology, Oncology and Palliative Medicine; Humans; K562; K562 Cells; Kinases; Laryngeal cancer; Leukemia; MAP Kinase Signaling System - physiology; Medical prognosis; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mortality; Phosphorylation; Proteins; raf Kinases - antagonists & inhibitors; raf Kinases - metabolism; Raf/MEK/ERK pathway; Signal Transduction - drug effects; STAT3; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Studies; Triterpenes - pharmacology; Raf/MEK/ERK pathway; K562; Leukemia; Cucurbitacin B; STAT3
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2009.07.015

Abstract Cucurbitacin B is a natural anti-cancer compound found in Cucurbitaceae. Although the anti-cancer activity of cucurbitacin B in human leukemia cells has been reported, the underlining mechanism is still unclear. To clarify its anti-cancer activity and the mechanism of action, five different leukemia cell lines (CCRF-CEM, K562, MOLT-4, RPMI-8226 and SR) of the National Cancer Institute panel were treated with cucurbitacin B. Leukemia cell growth was inhibited by cucurbitacin B with GI50 ranged from 15.6 nM to 35.3 nM and the growth inhibition effect was attributable to G2/M phase arrest and apoptosis. Western blotting analysis of cell signaling molecules indicated that cucurbitacin B inhibits STAT3 activation and the Raf/MEK/ERK pathway in the K562 cells.