Oleuropein, a Secoiridoid Derived from Olive Tree, Inhibits the Proliferation of Human Colorectal Cancer Cell Through Downregulation of HIF-1α

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.

Oleuropein induces apoptosis via activation of caspases and suppression of phosphatidylinositol 3-kinase/protein kinase B pathway in HepG2 human hepatoma cell line

“…Cardeno et al (14) reported that oleuropein limited cell growth and induced apoptosis in HT29 colorectal cancer cells through a p53-dependent pathway (14). A similar mechanism was also observed in breast cancer cells (12).…”

“…Andreadou et al reported that oleuropein is involved in cardiomyocyte metabolism through the activation of AMP-activated protein kinase α (AMPK) and suppression of inducible nitric oxide synthases (iNOS) (11). It has recently been reported that oleuropein may have therapeutic potential in a number of types of cancer, including breast cancer (12), thyroid cancer (13) and colorectal cancer (14), via inhibition of cell growth induction of apoptosis. However, to date the effects of oleuropein on liver cancer remain largely unknown.…”

Oleuropein Induced Apoptosis in HeLa Cells via a Mitochondrial Apoptotic Cascade Associated With Activation of the c-Jun NH2-Terminal Kinase

“…2, oleuropein induced accumulation of cells in the G 2 /M phase of the cell cycle, when the concentration of oleuropein was over 150 mM. However, some reports suggest that oleuropein induces G 1 arrest in several cell lines, including MCF-7, A549, and HT-29 cells (16,18,62). In MCF-7, olive leaves extract-treated cells was at G 1 arrest by the down-expression of Pin1 and c-Jun (66).…”

Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells

“…More recently, oleuropein has been investigated for its potent anti-cancer activity. It has been shown to inhibit proliferation and migration of a number of advanced grade human tumour cell lines in a dose dependent manner [6][7][8][9][10][11]. However, the effect of olive phenolic compounds has yet to be investigated for pancreatic cancer.…”