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Cancer is a leading cause of death in the United States, but new therapies targeting diet and lifestyle may aid in fighting the disease. Emerging research suggests that modulating the kind of nutrients available to cancer cells may encourage or inhibit their growth. Findings of a recent study detail the effects of polyunsaturated fats on cancer growth in mice.

Polyunsaturated fats are fatty acids that have more than one unsaturated carbon bond in the molecule, such as omega-3 and omega-6 fatty acids. They are present in fish, nuts, and seeds and are more prone to oxidation than other fatty acids. Polyunsaturated fats play critical roles in cardiovascular and neurological health.

While cancer is often viewed as a genetic disease, metabolic changes occur in cancer cells that contribute to their growth and spread. Cancer cells tend to produce energy by fermenting glucose to produce lactic acid, which acidifies the tumor environment, a phenomenon known as “cancer acidosis.” The acidity of the tumor environment alters the way cancer cells metabolize fats, increasing both the storage and the breakdown of fats.

Previous research demonstrated that targeting fatty acid metabolism may promote cancer cell death and prevent cancer spread by increasing lipid peroxidation (the breakdown of fats in the presence of iron) resulting in oxidative stress. Peroxidized lipids signal cellular damage, inducing a type of programmed cell death called ferroptosis (apoptosis occurring due to iron). However, it is unclear how different types of dietary fats affect cancer metabolism.

First, the authors of the present study exposed cervical, colorectal, and pharyngeal (throat) cancer cells to a variety of fats and measured the effects on metabolism. These fats included saturated fats, like those found in butter and palm oil; monounsaturated fats, like those found in olive oil; and polyunsaturated fats, including omega-6 fats, like those found in corn oil, and omega-3 fats, like those found in fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]). Next, they fed mice a diet supplemented with either olive oil or fish oil for four weeks. Two weeks into the diet, the mice developed cancer and the researchers measured the effects of the two diets on cancer progression. Finally, the researchers administered compounds to mice with cancer that induce or inhibit ferroptosis to further explore the mechanisms of cancer cell metabolism.

In cancer cells, exposure to both omega-6 and omega-3 polyunsaturated fats enhanced fat uptake and storage, which increased lipid peroxidation and induced ferroptosis to a greater extent than saturated or monounsaturated fats. Fats with the least saturation (meaning the most double bonds) were most effective, with the omega-3 fat DHA demonstrating the most cancer-fighting ability. However, this result only occurred in cancer cells with an acidic pH compared to a neutral pH. Mice that received the fish oil supplementation lost harmful white adipose tissue but gained metabolically beneficial brown adipose tissue, improving whole-body metabolism. The fish oil diet delayed cancer growth and increased survival, and this effect was magnified by the addition of a ferroptosis-inducing drug.

The authors of this important work concluded that polyunsaturated fats may be an effective add-on treatment to complement pharmacological therapies for cancer.

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