Oleocanthal is a natural phenolic compound found in extra-virgin olive oil. Specifically it is a phenylethanoid. Its chemical structure is related to oleuropein, also found in olive oil.
Figure 1: Oleocanthal molecular structure
Olecanthal is the sole phenolic compound that is responsible for the distinct irritation and pungency in extra virgin olive oil. When consuming fresh extra virgin olive oil, there can be a burning and stinging peppery sensation that occurs in the back of the throat which is due to the oleocanthal content. Extra virgin olive oil that is classified as “robust” contains the highest amounts of olecanthal.
The bitterness and pungency of oleocanthal in the throat often leads to coughing and throat clearing. In fact, high quality extra virgin olive oils are classified as either “one-cough”, two-cough” or “three-cough” oils. One-cough olive oil is considered good and is still extra virgin olive oil. A two-cough olive oil is better, where the oleocanthal levels are higher than a one-cough oil. The three-cough extra virgin olive oil is considered “exceptional” and has the highest levels of oleocanthal. Three-cough extra virgin olive oil has a “peppery” and “burning” sensation in the back of the throat. 1
Oleocanthal’s Wide Range of Biological Effects
Researchers have discovered through various studies that oleocanthal possesses a wide range of biological effects. Previous studies have reported its activity as: 2
- a potent antioxidant
- a nonsteroidal anti-inflammatory agent that inhibits COX-1 and COX-2
- a neuroprotectant that alters the structure and function of the neurotoxins β-amyloid and Tau
- an inhibitor of proliferation, migration, and invasion of human breast and prostate cancer cells through c-Met inhibition
- an inhibitor of AMPK in colon cancer cell
- an inhibitor of macrophage inflammatory protein-1α in multiple myeloma
A number of studies have shown that olecanthal possess some remarkable anti-cancer and chemopreventive properties.
Three studies from 2014, 2015 and 2016 demonstrate the antiproliferative activity of oleocanthal against breast and prostate cancer, colon cancer and malignant melanoma.
Oleocanthal has been reported to have strong anti-inflammatory properties. Oleocanthal has a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. 3
Oleocanthal demonstrated that the EVOO extracts tested showed an antiproliferative effect on colon cancer cells through the interaction with estrogen-dependent signals involved in tumor cell growth. 4
Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). 5
Oleocanthal Kills Cancer Cells In Vitro
A recent study from January 2015 has shown that oleocanthal is capable of killing a variety of human cancer cells in vitro (in the laboratory) while leaving healthy cells unharmed. 6 The researchers focused on breast, pancreatic, and prostate tumor cells. They applied oleocanthal to these cancer cells and discovered that the cancer cells were dying very quickly – within 30 minutes to an hour. Normal programmed cell death, known as apoptosis, usually takes between 16 and 24 hours to complete its process.
What they found was that oleocanthal pierces cancer cells’ lysosomes, the organelle in the cell cytoplasma that store the cell’s waste products, releasing enzymes that kill the cell. Oleocanthal caused a temporary halt in the life cycle of non-cancerous cells for a 72 hour period at which time they returned (awakened) to their normal proliferation, thus sparing the healthy cells from programmed cell death.
Figure 2: Location of the Lysosome in the human cell
The lysosomes act as the waste disposal system of the cell by digesting unwanted materials in the cytoplasm, both from outside of the cell and obsolete components inside the cell. Material from the outside of the cell is taken-up through endocytosis, while material from the inside of the cell is digested through autophagy.
Figure 3: Anatomy of the Lysosome
Lysosomal membranes of cancerous cells are weaker than those of non-cancerous cells, so inducing apoptotic cell death of permeable lysosome membranes may kill the cancerous cells. This is exactly what the researchers discovered was happening when oleocanthal was applied to cancerous cells. Oleocanthal mediated cancer cell death is promoted by destabilization of the lysosomal membrane, leading to the induction of lysosomal membrane permeabilization (LMP).
Effectively, the oleocanthal punctured the weak and destabilized lysosome cell membrane which then killed the cancerous cells via their own enzymes. Healthy cells avoided being punctured by oleocanthal since their lysosome cell membrane was strong and stable.
The researchers concluded their study with the promising statement: 7
“Compounds that induce lysosomal membrane destabilization, such as OC, represent a viable method to exploit the vulnerability of the enlarged lysosomes in cancer cells. Our data suggest that the chemopreventive activity of EVOO is due to the ability of its bioactive phenolic components, especially OC, to induce cell death by entering the lysosome and inhibiting ASM activity, which induces LMP. Therefore, the ability of OC to induce LMP in cancer cells, but not normal cells, represents a novel therapeutic strategy for treating a large number of cancer types in which lysosomes are enlarged and more sensitive to lysosomotropic agents.”