Olive Oil Could Fight Cancer via CB1 Receptors

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Dietary Olive Oil Could Fight Cancer Through CB1 Receptors

Research has shown that adherence to the Mediterranean diet can lead to longer lives, stronger bones, lower risk of cardiovascular disease, and lower risk of cancer. Generally, the diet emphasizes eating mostly plant-based foods (such as fruits, legumes, and unrefined grains), moderate protein (mostly fish and little to no red meat), small amounts of wine, and of course, olive oil.

Olive oil consumption in particular represents one of the most important contributions to the beneficial effects on health of the Mediterranean diet and may be key in cancer prevention. Studies show fairly conclusively that populations within the Mediterranean basin enjoy a healthy lifestyle with decreased incidence of degenerative diseases including cancer and cardiovascular disease. In these regions olives are liberally consumed and olive oil is the cooking and garnishing fat of choice.

The latest research into oleic acid — the primary ingredient in olive oil — has shown how it can help prevent cancer-causing genes from functioning in cells, and may help to prevent cancer developing in the brain. High concentrations of phenolic antioxidants and squalene in olive oil may help prevent cancer as well. A continuous supply of antioxidants reduces oxidative stress and inhibits the formation of DNA adducts, which are factors that are linked to a host of diseases including breast and colon cancer. Because squalene is to a large extent transferred to the skin, it’s thought to help protect against skin cancer.

Interestingly, olive oil has been shown to interact with the endocannabinoid system (ECS) as well. In fact, research into olive oil’s effects on CB1 receptors could have an impact on the fight against colon cancer.

Extra Virgin Olive Oil and the CB1 Receptor

Although the process known as methylation is involved in regulating gene expression, aberrant or abnormal gene expression has been linked to cancer. How does that happen?

Well, DNA methylation (when methyl groups are added to the DNA molecule) can change the activity of a DNA segment without changing the sequence. When this happens at a gene “promoter” site/region where transcription occurs (the region where DNA is normally turned into RNA), DNA methylation typically acts to repress gene transcription. These activities affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer.

However, in a study published in the Journal of Nutritional Biochemistry in 2014, a team of Italian and Swedish researchers wanted to investigate the potential role of extra virgin olive oil (EVOO) as a preventive antitumor agent. They also wanted to see whether it would be able to influence epigenetic processes that are known to participate in cancer development and likely influence its progression. More specifically, they wanted to see how dietary EVOO and two of its phenolic compounds would affect CNR1 gene expression (CNR1 is the gene coding for the CB1 receptor) in human colon cancer cells, as well as in the colon mucosa (mucous membrane) of rats. The two phenolic compounds tested were an olive oil phenolic extract (OPE), and hydroxytyrosol (HT) which is a type of phenolic phytochemical with antioxidant properties.

Their results produced several important insights.

The researchers showed that EVOO and its phenolic components were able to increase CNR1 gene expression in colon cancer cells as well as in the rat colon.

Additionally, they also observed that CB1 receptors were silenced in colon cancer cells due to high DNA methylation, which is something you don’t see in normal colon mucosa cells. Less CB1 expression means lower endocannabinoid tone while high DNA methylation is also a relevant mechanism for cancer progression.

These in vitro studies were subsequently confirmed in vivo when they extended their investigation into colon samples of rats.

They found that DNA methylation at the CNR1 promoter site of rat colon was comparable to that observed in normal colon mucosa cells. However, rats that were treated with EVOO for 10 days showed an increase in CNR1 gene expression and protein levels in their colon, an effect partly associated to a reduction in DNA methylation at CNR1 promoter. These results mirrored the results they observed earlier with human colon cancer cells.

Finally, to further investigate mechanisms by which EVOO determined the induction of CB1 in vivo, the team investigated the expression of four miRNAs, previously shown to be involved in the pathogenesis of colorectal cancer. Both miR23a and miR301a expression was found to be selectively reduced after either single or 10-day EVOO administration.

Implications Of The Study

In conclusion, the team of researchers were able to provide evidence that EVOO had a powerful effect on cancer causing mechanisms – mainly DNA methylation of the endocannabinoid receptor CB1. Although further studies are required, their data supports a potential role of EVOO as a preventive antitumor agent that can modulate epigenetic processes that lead to cancer development and progression.

EVOO may also provide a new therapeutic strategy for the treatment of cancer as well.

For example, endocannabinoids such as anandamide and 2-AG may play a role in combating tumor growth but increased levels of endogenous cannabinoids might not affect tumor growth because of the loss of CB1 in most human colorectal cancers. Lower CB1 levels would make these cells resistant to anandamide and 2-AG. However, an initial treatment with an EVOO compound to boost CB1 levels followed by administration of a CB1 agonist to achieve optimal stimulation of apoptosis might be effective.

Again, these theories would need to be explored and studied. But nevertheless, the potential cancer-preventative effects of extra virgin olive oil – through it’s effects on CB1 expression – is a promising new discovery that’s worthy of further exploration.

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