Reactive oxygen species are reactive molecules what contain oxygen. In cells they are formed as a by-product during the metabolism of oxygen. These metabolites often play important roles in the body such as call signaling and regulation. These reactive oxygen species often contain free radicals which are known to be harmful in high concentrations. Their concentrations are significantly higher under stressful conditions such as UV light. Selenium actively helps to combat this oxidative stress making it a viable target for anti-cancer therapy.
Selenium acts by multiple, complementary pathways to prevent cancers from developing. This pleiotropy allows selenium to attack cancer in many different ways. Detailed studies have revealed that there are 12 distinct mechanisms by which selenium prevents potentially cancerous cells from achieving full tumor status:
- Regulation of lipoxygenases, enzymes that produce inflammatory molecules that promote cancer growth;
- Direct reduction of oxidative stress that causes free radical damage;
- Protection of the antioxidant-recycling selenoproteins;
- Detoxification of cancer-inducing metals;
- Induction of protective 'phase II' liver enzymes that neutralize organic carcinogenic toxins;
- Inhibition of DNA alterations, precursors to initiation of cancerous changes;
- Inactivation of molecular transcription factors required by cancer cells to support their growth and development;
- Shutting down of the essential cell replication cycle needed by cancer cells to produce their explosive growth;
- Induction of apoptosis, the programmed cell death, a natural feature of all normal body cells that is missing in cancerous cells, allowing them to continue to reproduce indefinitely;
- Enhanced immune system activity to detect and destroy incipient cancer cells;
- Downregulation of sex hormone receptors used by certain cancers to sustain their growth;
- Limiting effects on tumor invasion and metastasis.
Selenium exists in many different forms, all of which have different anti-cancer mechanisms and properties. These are 3 of the main forms of selenium that are used in anti-cancer therapy: sodium selenite, L-selenomethionine, and selenium-methyl L-selenocysteine. Each form offers a different approach to cancer therapy.
Sodium selenite is an inorganic mineral that we naturally consume in our diet. There are some studies that suggest inorganic selenium is less bioactive than its other forms however other studies suggest there is little effect in the form of selenium on the body’s ability to process it and convert it to selenoproteins. However Inorganic selenium has been shown to be more effective at increasing genetic expression in anti-oxidant enzymes, including the selenium containing glutathione peroxidase. Despite this it is actually incorrect to consider sodium selenite as an antioxidant, it simply helps stimulate an immune response and assist in DNA repair.
Sodium selenite is an effective anti-cancer agent. Through a variety of mechanisms, it has been shown to destroy many different types of cancer including lung, bone, cervical, liver and leukemia amongst others. Its most effective mechanism is to target the reactive oxygen system and selectively target the mitochondria in cancer cells whilst not harming the healthy cells.
Another mechanism utilized by sodium selenite is to target the Bcl-2 protein. The Bcl-2 gene is involved in regulation of cell death. As it is known to be expressed in much higher levels in cancer cells, thus targeting this protein is an effective method of inducing cell death by apoptosis. In a randomized controlled clinical trial where patients with aggressive head and neck cancers received 200 mcg per day of sodium selenite, patients showed an increased ability to destroy tumor cells, resulting from an increased immune response potentially triggered by an increase in selenium. This combined with other studies suggests that inorganic selenium, such as selenium selenite has the potential to be a very effect anti-cancer therapy.
Other inorganic forms of selenium have also been shown to have a positive anti-cancer effect. One of these is selenium dioxide. Selenium dioxide is also believed to induce cancer cell apoptosis and inhibition of telomerase enzyme activity. A study found there was a reduction meaning it has potential to be another viable anti-cancer therapy.
In contrast to inorganic selenium selenite, L-selenomethionine is an organic complex of an amino acid (methionine) but with the sulfur replaced by selenium. It is this form of selenium that is commonly found in food such as nuts and cereals. It is absorbed by the body more readily than its inorganic counterpart.
Studies have showed that L-selenomethionine inhibits the growth of cancer cells at rates more than a thousand times greater than it does cells in healthy normal tissue. This finding is one of reasons that L-selenomethionine is considered to have an excellent safety profile.
L-selenomethionine also used in gene therapy cancer treatment. By using enzymes, selenomethionine can be converted to methylselenol by an α,γ-elimination. This process can then be targeted by a gene-directed enzyme cancer pro-drug. This therapy works by targeting the faulty p53 proto-oncogene which codes for cell regulation, which is key to suppressing cancer. It is also involved in apoptosis making it a viable candidate for cancer suppression as it can prevent mutated cells from surviving.
L-selenomethionine is accredited with being the reason for the major upturn in research into selenium as a viable anti-cancer therapy, however it has been shown to be a less effective anti-cancer agent than other forms of selenium. This is potentially due to how the selenium enters the cells. I tis believe that to properly convert the selenomethionine to selenols the selenium must be ingested and processes through the digestive system to reach cells. This this case the inorganic selenium is more readily absorbed into the blood stream. However, this is only effect truly effective when methionine is the excess, otherwise the selenium is used up in replacing low methionine in the proteins of the cells and not available for cancer prevention.
Selenium-methyl L-selenocysteine is an organic complex of selenium, in with the normally sulfur containing amino acid L-cysteine has its sulfur substituted for a selenium. Relative to other forms of selenium anti-cancer research this the youngest and most novel. This form of selenium occurs natural in plants from the allium family such as common household ingredients: onions and garlic. As for most food stuffs the level of selenium in the soil in which it is grown has a massive impact upon the selenium levels of the resulting plants, therefore when grown in selenium rich soils these allium plants contain one of the most potent forms of selenium known.
As with other forms of selenium, this form is known to exhibit its anti-cancer effects by promoting self-induced cell suicide by cell apoptosis. Selenium-methyl L-selenocysteine also downregulates expression of Bcl-2 protein, important in cell regulation, allowing for rapid destruction of cancer cells.
Selenium is this form acts differently to others. Like other forms it also targets regulatory proteins, but more specifically targets proteins involved in maintaining normal circadian rhythms. Restoration of these proteins allows for treatment of breast cancer by regulating the levels of melatonin and estrogen.
In a very different approach to other forms of selenium it can target the growth of new blood vessels. This can effectively stifle tumor growth by removing their oxygen and nutrient supply. It can also promote the delivery of chemotherapy drugs to the location of the tumor. This effect potentially allows it to be effective when combined with other anti-cancer agents. Studies have shown selenium-methyl L-selenocysteine to be particularly effective when combined with breast cancer drugs. In particular tamoxifen. Mice with the MCF-7 breast cancer xenograft and the underlying mechanisms displayed significant reduction in tumor growth when combining selenium-methyl L-selenocysteine and tamoxifen.
To conclude, selenium is an effective anti-cancer agent in many ways. It is an essential micronutrient, vital to maintaining a healthy lifestyle and body. And whilst the true benefits might not yet to clear, it seems that taking selenium in either an organic yeast modified form or a more common inorganic supplement may also play a role in helping the body fight cancer through immune responses.
But by far the promising aspect of selenium as when administered as a treatment either by itself or alongside another pro-drug. The most interesting case for this is Clarke’s infamous 1996 study. Initially his results presented that selenium had little to no effect on the treatment of 2 types of skin cancer. However, it was later discovered that his findings lead to a much greater reduction of other forms of cancer in his trial patients. There was in fact a 50% reduction in patients, which was so impressive the blinded phase of the trail was stopped early to allow patients the maximum benefits.
With further research to fully understand the benefits of the various different forms of selenium, including: selenium selenite, L-selenomethionine and Selenium-methyl L-selenocysteine, and the 12 known mechanisms in which they interact within the body it should make for a very effect anti-cancer therapy and great improve the lives of thousands of cancer patients, suffering from a wide range of cancers, in the near future.