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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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.
Hao K. New compounds from the seeds of Embelia ribes Burm. Pharmazie. 2005;60(1):69–71.
Joshi R. Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chem Biol Interact. 2007;167(2):125–34.
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.
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].
Podolak I. Cytotoxic activity of embelin from Lysimachia punctata. Fitoterapia. 2005;76(3–4):333–5.
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.
Mori T. Effect of the XIAP inhibitor embelin on TRAIL-induced apoptosis of pancreatic cancer cells. J Surg Res. 2007;142(2):281–6.
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.
Fukuda S. Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther. 2006;5(5):1087–98.
Tamm I. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000;6(5):1796–803.
Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 2002;9:459–70.
Lu M. XIAP induces NF-κB activation via the BIR1/TAB 1 interaction and BIR1 dimerization. Mol Cell. 2007;26:689–702.
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.
Ni T. The ubiquitin ligase ability of IAPs regulates apoptosis. IUBMB Life. 2005;57(12):779–85.
Danquah M. Micellar delivery of bicalutamide and embelin for treating prostate cancer. Pharm Res. 2009;26(9):2081–92.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hu, R., Zhu, K., Li, Y. et al. Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells. Med Oncol 28, 1584–1588 (2011). https://doi.org/10.1007/s12032-010-9601-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-010-9601-5