Selenium is an essential trace element that is of considerable importance to human health, including muscle function, male reproduction, cardiovascular, endocrine, nervous system and especially the immune system. Selenium levels outside the recommended range have been linked to infertility and many other human diseases due to their involvement in thyroid hormone regulation.
Selenium also regulates immune functions through the redox regulation of selenoproteins (e.g., glutathione peroxidase), protects immune cells from oxidative stress, and protects against DNA damage. Therefore, selenium has great potential in cancer prevention and treatment.
1. Selenium dosage and cancer
The effect of Se on malignant transformation, tumor growth and progression is dependent on the concentration/dose and chemical form of the selenium compounds. The three most important forms of Se compounds in cancer prevention are sodium selenite (Na2SeO3), l-selenomethionine (C5H11NO2Se) and Se-methylselenocysteine, which differ in metabolic pathways and reduce cancer risk. For example, l-selenomethionine is better absorbed than sodium selenite. However, selenite is more cytotoxic than Se-methylselenocysteine and selenomethionine.
In summary, biologically, Se serves as a double-edged sword, at low concentrations or at nutritional levels as an antioxidant via selenoprotein, eliminating ROS, supporting cell survival and growth. At higher pharmacological doses or supernutrient levels, Se acts as an antioxidant that induces ROS and induces cell death.
In cancer, studies have been done mainly on the benefits of Se intake in reducing cancer risk at the nutritional level; however, fewer studies have explored the effects of supernutrient or pharmacological doses of Se on cancer.
2. Cancer prevention at nutritional level
Accumulating evidence suggests a chemopreventive role of Se in cancer risk and incidence. At the nutritional level, defined as sufficient amounts to saturate selenoproteins, Se functions as an antioxidant and plays a chemopreventive role against cancer through scavenging of oxidative radicals; thus, preventing DNA damage and the occurrence of mutations.
The effect of Se status on cancer has been investigated in several human clinical trials and epidemiological studies. The study showed a beneficial effect of higher Se status in preventing the recurrence of lung cancer and patients with different types of cancer.
Furthermore, the cancer prevention nutrition trial demonstrated that Se-rich yeast reduces the incidence and mortality of colorectal, prostate and lung cancers. An intervention study of more than 300 cancer patients in 2019 found that serum Se levels above 69 μg/L were significantly associated with improved survival.
3. Chemotherapy at the super nutrient level
In contrast, supernutrient levels or pharmacological doses of redox-active Se compounds (e.g. selenite) or redox-active Se metabolites (e.g. selenide) both react with thiols and oxygen to induce oxidative stress, that is, pharmacological dosage of Se plays a pro-oxidative anticancer role.
For example, drug-resistant malignant cells (such as lung cancer cells) are more sensitive to pharmacological doses of selenite than normal cells. Proposed mechanisms targeting the resistance model include increased thiols levels, generation of redox enzymes, higher metabolic rates, increased metabolism, and elimination of xenobiotics (foreign molecules such as cytotoxic drugs).
These mechanisms involve membrane pump channels such as the multidrug resistance protein (MRP) superfamily, the xc − cystine/glutamate antiporter system, and high intracellular glutathione levels. That is, an increase in the rate of Se uptake leads to a higher accumulation of Se in malignant cells compared with normal cells.
Higher intracellular concentrations of glutathione and thiol, together with higher metabolic rates and oxygen delivery in the tumor microenvironment (TME), facilitate redox cycles between selenide or monomethylselenol, oxygen and thiol, which leads to stoichiometric oxidative stress in tumor cells.
Overall, Se has great potential to be used as a cancer chemotherapeutic, but so far, only a few clinical trials have been conducted to evaluate the pharmacological effects of Se in cancer. In 2015, a first systematic human phase I clinical trial using sodium selenite in cancer patients (IV to terminal) showed high tolerance and the maximum tolerated dose was determined to be 10.2 mg/m2 body surface area.
References:
- A. Razaghi, M. Poorebrahim, D. Sarhan, and M. Björnstedt, “Selenium stimulates the antitumour immunity: Insights to future research”, European Journal of Cancer, vol 155, pp 256–267, September 2021, doi: 10.1016 /j.ejca.2021.07.013.
- O. Brodin et al., “Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study”, Nutrients, vol 7, p.h 6, pp. 4978–4994, June 2015, doi: 10.3390/nu7064978.
- S. Pietrzak et al., “Influence of the selenium level on overall survival in lung cancer”, J Trace Elem Med Biol, vol 56, pp 46–51, December 2019, doi: 10.1016/j.jtemb.2019.07.010.
Article source: Nutrition Research and Development Institute (https://inrd.vn/)
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