Mammalian cells synthesize cholesterol through a series of reaction steps containing 21 enzymes, among which many metabolic intermediates are produced, which play an important role in physiology and development. Cholesterol itself is a precursor of steroid hormones and sterols, the latter can be further modified into molecules that can induce special biological responses.
Epidemiological studies have pointed out the role of cholesterol in the risk of breast cancer, and recent research has also shown that there is some new relationship between cholesterol metabolism and breast cancer: certain cholesterol metabolites can promote or inhibit breast cancer. This raises important new questions on how to regulate or inhibit cholesterol metabolism pathways and which pathways can treat cancer.
Last year, researchers from Duke University discovered that a by-product of cholesterol acts like an estrogen, driving the growth and spread of the most common types of breast cancer. They also confirmed that cholesterol-lowering drugs such as statins seem to reduce the effects of this hormone-like molecule.
This is a very important research finding. Because human breast cancer expresses 27HC-producing enzymes, the estrogen-like molecules they produce promote tumor growth. In essence, the tumor forms a mechanism to use different fuels. And these findings suggest that the use of statins or a healthy diet to suppress cholesterol may be a simple way to reduce the risk of breast cancer. In addition, for breast cancer women with high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors.
At the same time, another Cell Report article also pointed out that cholesterol metabolism can be used as a potential stimulant for breast cancer, that is, cholesterol metabolites can induce breast cancer that is positive for estrogen receptors.
Researchers have discovered that a cholesterol metabolite (27HC) called 27-hydroxycholesterol can promote tumor growth in individuals with estrogen receptor-positive breast cancer, which is a common breast cancer disease; the disease has previously been It is believed to be caused by female estrogen, and is usually treated with endocrine-based drugs.
But there are also studies that found that cholesterol metabolites can inhibit breast cancer. In an article published in Nature Communications entitled "Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties", the researchers found that A metabolite called Dendrogenin A can stimulate breast cancer cells to redifferentiate (restored normal physiological function), which has been confirmed in vitro and in vivo experiments, and the survival rate in animal models has also increased.
Interestingly, this cholesterol metabolite is less in breast cancer patients than in normal cells, which means that the regulation of dendrogenin A biosynthesis is abnormal during canceration, and the specific molecular mechanism is still unclear .
Understanding the balance mechanism between cholesterol and cancer development will help to analyze the pathological mechanism of breast cancer and other cancers, and also bring new hope for more effective treatments.
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