February 22, 2024

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Palmitic Acid in Diet Accelerates Cancer Cell Metastasis

Palmitic Acid in Diet Accelerates Cancer Cell Metastasis



Palmitic Acid in Diet Accelerates Cancer Cell Metastasis

Palmitic acid (PA) is the most common saturated fatty acid in the human body, accounting for 20-30% of total fatty acids. On average, a person weighing 70 kilograms consists of 3.5 kilograms of palmitic acid. It can be obtained from diet or synthesized in the body.

Palmitic acid is widely present in our daily diet.

Palmitic acid accounts for 44% of the total fat in palm oil, which, being completely free of genetically modified components and having a tenfold higher oil yield per unit area compared to other oilseeds, has surpassed soybean oil to become the world’s most important edible vegetable oil.

Palm oil is widely used in the food processing industry: candies, cakes, cheese analogs, potato chips, chocolates, biscuits, frozen foods (pancakes, pies, pizzas), ice creams, instant noodles and oatmeal, margarine, peanut butter, salad dressings, hot pot bases, etc.

In addition, palmitic acid is also present in many meats and dairy products (constituting 50-60% of total fat), cocoa butter (26% of total fat), olive oil (8-20% of total fat), and even breast milk (20-30% of total fat).

For a long time, there has been no consensus on whether palmitic acid is harmful to health. A report from the World Health Organization (WHO 2003) suggests that palmitic acid increases the risk of cardiovascular diseases, but some experimental results do not support this conclusion. The controversy in results may stem from the complexity of diets, differences in experimental selection criteria, and the age of the subjects.

A recent article published in Nature indicates that palmitic acid alters the epigenome of mice and promotes the metastasis of cancer cells in mice.

Researchers stimulated oral squamous cell carcinoma (OSCC) cells with 300μM concentration of palmitic acid (PA), 50μM concentration of oleic acid (OA), or 50μM concentration of linoleic acid (LA) in vitro for 4 days, and then inoculated these cells in situ into mice fed a standard diet.

Palmitic Acid in Diet Accelerates Cancer Cell Metastasis

The results showed that mice inoculated with OSCC cancer cells stimulated by palmitic acid had a significantly increased number and size of metastatic lesions in their bodies, while oleic acid and linoleic acid did not have this effect.

Moreover, researchers found that this enhanced metastasis did not require continuous stimulation by palmitic acid. After stimulating OSCC cancer cells with palmitic acid in vitro for 4 days, researchers found that when these stimulated cancer cells were cultured in standard medium for 14 days, they still retained high metastatic ability! This indicates that short-term stimulation with palmitic acid can maintain the strong metastatic ability of cancer cells for a long time.

So, do foods containing palmitic acid also promote cancer cell metastasis?

Next, they inoculated OSCC cancer cells into mice and waited for the formation of primary tumors, then fed these cancer-bearing mice with foods rich in palm oil for a short period, with cancer-bearing mice fed with foods rich in olive oil or standard diet as controls, and after 10 days, all were switched to a standard diet.

To observe the metastatic results more clearly, they extracted primary tumors from mice and purified them, then transplanted these purified cancer cells into secondary mice fed with a normal diet.

The results showed that tumor cells from primary mice had stronger metastatic abilities in secondary mice fed with palm oil than those fed with olive oil or a standard diet. This indicates that foods containing palmitic acid also promote cancer cell metastasis.

Cell behavior is controlled by gene expression, so have the epigenomes of cancer cells stimulated by palmitic acid changed, leading to changes in gene expression?

Researchers analyzed the epigenome of OSCC cancer cells treated with palmitic acid in vitro and found stable changes in H3K4me3, thereby mediating the expression of genes related to neurogenesis, neural remodeling, extracellular matrix (ECM) organization, and gliogenesis, which have been shown to be associated with poor cancer prognosis.

H3K4me3 is a trimethylation mark on the fourth lysine residue of histone H3, mainly responsible for gene activation. Histone modifications such as methylation and acetylation can be inherited by offspring cells, so the changes in H3K4me3 induced by palmitic acid treatment can be transmitted to its daughter cells during cancer cell division. This is also why cancer cells still retain strong metastatic ability after stopping palmitic acid stimulation.

In conclusion, this study confirms that dietary palmitic acid not only promotes cancer cell metastasis but also passes on this metastatic ability to their offspring, allowing this strong metastatic ability to persist.

Seeing this, many people may want to discard processed foods containing palm oil, such as instant noodles and hot pot bases. Eating less processed foods is definitely a good idea, but even if we avoid palm oil, milk and meat we consume daily contain a considerable amount of palmitic acid. Does this affect our health?

Fatty acids (such as palmitic acid) are important components of the diet and participate in many crucial physiological activities in the body: ensuring the physical properties of cell membranes, palmitoylation of proteins, biosynthesis of palmitoylethanolamide (PEA), and effective surfactant activity in the lungs, among others.

Under normal circumstances, the content of palmitic acid in tissues seems to be controlled within a specific range. According to literature reports, the average daily intake of palmitic acid by humans is about 20–30 grams, and variations in intake do not significantly affect its tissue concentration because dietary palmitic acid balances with de novo lipogenesis (DNL) of palmitic acid in the body, thereby maintaining the steady state of its tissue concentration.

However, under certain specific factors, such as excessive intake of carbohydrates (especially monosaccharides and disaccharides) and a sedentary lifestyle, excessive accumulation of palmitic acid in tissues may occur, which may lead to lipid disorders, high blood sugar, and increased ectopic fat accumulation; or under certain pathological conditions, palmitic acid may further accelerate its harmful effects on the body.

Just as in the aforementioned Nature study, palmitic acid does not induce cancer in mice, but it accelerates the metastasis of cancer cells in mice with existing cancer. Therefore, moderation is key, and maintaining a balanced diet and good lifestyle habits is undoubtedly evidence-based for promoting health!

Palmitic Acid in Diet Accelerates Cancer Cell Metastasis


References:

Salvador Benitah, Dietary palmitic acid promotes a prometastatic memory via Schwann cells, Nature (2021). DOI: 10.1038/s41586-021-04075-0. www.nature.com/articles/s41586-021-04075-0

(source:internet, reference only)

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