Advertisement

Medical Oncology

, Volume 28, Issue 4, pp 1584–1588 | Cite as

Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells

  • Rong Hu
  • Ke Zhu
  • Yingchun Li
  • Kun Yao
  • Rong Zhang
  • Huihan Wang
  • Wei Yang
  • Zhuogang LiuEmail author
Original Paper

Abstract

The present study was undertaken to determine the molecular mechanisms by which embelin induces apoptosis in human leukemia cells. Embelin resulted in loss of cell viability and inhibition of proliferation in a dose- and time-dependent manner, which was largely attributed to apoptosis. Embelin caused depolarization of mitochondrial membrane potential. Western blot analysis showed that the expression of anti-apoptotic proteins X-linked inhibitor of apoptosis (XIAP) was down-regulated by embelin. Embelin induced activation of caspase-9 and embelin-induced apoptosis was prevented by caspase inhibitors. Taken together, these findings suggest that embelin results in human leukemia cells apoptosis through caspase-dependent mechanisms involving down-regulation of XIAP.

Keywords

Embelin Apoptosis X-linked inhibitor of apoptosis Leukemia 

References

  1. 1.
    Ahn KS. Embelin an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein, blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Mol Pharmacol. 2007;71(1):209–19.PubMedCrossRefGoogle Scholar
  2. 2.
    Hao K. New compounds from the seeds of Embelia ribes Burm. Pharmazie. 2005;60(1):69–71.PubMedGoogle Scholar
  3. 3.
    Joshi R. Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chem Biol Interact. 2007;167(2):125–34.PubMedCrossRefGoogle Scholar
  4. 4.
    Sreepriya M. Effects of administration of embelin and curcumin on lipid peroxidation, hepatic glutathione antioxidant defense and hematopoietic system during N-nitrosodiethylamine/Phenobarbital-induced hepatocarcinogenesis in Wistar rats. Mol Cell Biochem. 2006;284(1–2):49–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Singh D. Effects of embelin on lipid peroxidation and free radical scavenging activity against liver damage in rats. Basic Clin Pharmacol Toxicol. 2009. [Epub ahead of print].Google Scholar
  6. 6.
    Podolak I. Cytotoxic activity of embelin from Lysimachia punctata. Fitoterapia. 2005;76(3–4):333–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Siegelin MD. The XIAP inhibitor embelin enhances TRAIL-mediated apoptosis in malignant glioma cells by down-regulation of the short isoform of FLIP. Neurochem Int. 2009;55(6):423–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Mori T. Effect of the XIAP inhibitor embelin on TRAIL-induced apoptosis of pancreatic cancer cells. J Surg Res. 2007;142(2):281–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Denizot F. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986;89(2):271–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Fukuda S. Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther. 2006;5(5):1087–98.PubMedCrossRefGoogle Scholar
  11. 11.
    Tamm I. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000;6(5):1796–803.PubMedGoogle Scholar
  12. 12.
    Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 2002;9:459–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Lu M. XIAP induces NF-κB activation via the BIR1/TAB 1 interaction and BIR1 dimerization. Mol Cell. 2007;26:689–702.PubMedCrossRefGoogle Scholar
  14. 14.
    Jantova SL. 3-(5-Nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4] triazolo [4,3-c] quinazoline induces ROS-mitochondrial mediated death signaling and activation of p38 MAPK in murine L1210 leukemia cells. Neoplasma. 2009;56(6):494–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Ni T. The ubiquitin ligase ability of IAPs regulates apoptosis. IUBMB Life. 2005;57(12):779–85.PubMedCrossRefGoogle Scholar
  16. 16.
    Danquah M. Micellar delivery of bicalutamide and embelin for treating prostate cancer. Pharm Res. 2009;26(9):2081–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Rong Hu
    • 1
  • Ke Zhu
    • 1
  • Yingchun Li
    • 1
  • Kun Yao
    • 1
  • Rong Zhang
    • 1
  • Huihan Wang
    • 1
  • Wei Yang
    • 1
  • Zhuogang Liu
    • 1
    Email author
  1. 1.Department of Hematology, Shengjing HospitalChina Medical UniversityShenyangChina

Personalised recommendations