Journal
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
Volume 1814, Issue 10, Pages 1340-1348Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbapap.2011.05.015
Keywords
Sulforaphane; Proteomic analysis; 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatases; Hypoxia-inducible factor-1; Mitogen-activated protein kinase
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Funding
- ARPC, Korea [20090194]
- Han Cell Inc.
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The anti-cancer activity of sulforaphane (SFN) has recently been investigated in several cancer cell lines, including human hepatic cancers. However, the mechanism of SFN-induced cell death in human hepatic cancer cells is still not well understood. The aim of the present work is to explore the possible mechanisms of SFN-induced apoptosis in hepatocellular carcinoma cells using proteomic analysis. A two-dimensional electrophoresis (2-DE)-based-proteomic analysis was employed for identification of possible target-related proteins of SFN-induced apoptosis. Among eleven proteins identified as regulated, we focused on the downregulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase4 (PFKFB4) protein, which has been known as a key modulator of glycolysis. We also showed that SFN down-regulated the expression of the transcriptional factor, hypoxia inducible factor-1 alpha (HIF-1 alpha), which strongly regulates PFKFI34 expression. In order to obtain a broad understanding of the correlation of HIF-1a and SFN, we observed the inhibition of the activity of mitogen-activated protein kinases, regulators of HIF-1a activity. Our findings suggest that SFN is a potent inducer of apoptosis in hepatocellular carcinoma cells via PFKFB4-inhibition pathways. HIF-1 pathway inhibition may be mediated by the inhibition of mitogen-activated protein kinases. (C) 2011 Elsevier B.V. All rights reserved.
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