Oleuropein, a Secoiridoid Derived from Olive Tree, Inhibits the Proliferation of Human Colorectal Cancer Cell Through Downregulation of HIF-1α
- 31 January 2013
- journal article
- research article
- Published by Informa UK Limited in Nutrition and Cancer
- Vol. 65 (1), 147-156
- https://doi.org/10.1080/01635581.2013.741758
Abstract
Oleuropein (OL) is the most prominent phenolic compound in the fruit of olive tree. Although OL has shown powerful anticancer activity the underlying action mechanism remains largely unknown. The present study evaluated the effects of OL on hydroxityrosol (HT)-29 human colon adenocarcinoma cells in comparison to hydroxytyrosol, its hydrolysis product, and to elucidate the underlying anticancer molecular mechanisms involved. Cell proliferation was determined using SRB assay. Cell cycle and apoptosis were assessed by flow cytometry and changes in MAPK cascade protein expression, HIF-1α, p53, PPARγ, and NFKβ signaling pathways by Western blot. Although OL showed less potency than HT, in terms of cell growth inhibition, induced significant changes in cell cycle analysis and caused a significant increase in the apoptotic population. Both compounds produced a remarkable decrease in HIF-1α protein and an upregulation of p53 protein expression. However, no significant changes in IkB-α and MAPK cascade protein expressions were observed. HT produced a significant upregulation in peroxisome proliferator-activated receptor gamma (PPARγ) expression whereas OL failed. PPARγ upregulation may be one of the principal mechanisms of the tumor shrinkage by HT. Our novel findings demonstrate that OL limits the growth and induces apoptosis in HT-29 cells via p53 pathway activation adapting the HIF-1α response to hypoxia.Keywords
This publication has 29 references indexed in Scilit:
- Apoptotic cell signaling in cancer progression and therapyIntegrative Biology, 2011
- Thiocolchicoside Exhibits Anticancer Effects through Downregulation of NF-κB Pathway and Its Regulated Gene Products Linked to Inflammation and CancerCancer Prevention Research, 2010
- “Where, O Death, Is Thy Sting?” A Brief Review of Apoptosis BiologyMolecular Neurobiology, 2010
- Effects of olive oil polyphenols on fatty acid synthase gene expression and activity in human colorectal cancer cellsGenes & Nutrition, 2010
- Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeuticsOncogene, 2009
- Association between Mediterranean dietary patterns and cancer riskNutrition Reviews, 2009
- Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cellsCytotechnology, 2009
- tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO)BMC Cancer, 2008
- The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cellsOncogene, 2008
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976