Vitamin E and Cancer

Abstract
Vitamin E is one of the most researched compounds in the medical community because of what is believed to be its ability to prevent and effectively treat cancer. There are eight forms of vitamin E, of which gamma-tocopherol and tocotriencols have shown the greatest promises in effectively treating and preventing cancer. However, simply taking large amounts of vitamin E is not likely to be effective at preventing and reducing the risk of cancer. Research has shown Gamma-tocopherol has been effective at treating both breast cancer cells and colon cancer cells because it induces apoptosis in the cancerous cells without harming non-cancerous cells. In comparison, Tocotriencols may be even more effective than gamma-tocopherol because of greater cellular accumulation. This is particularly true in the treatment of breast cancer because of estrogen receptor signaling. For both types of vitamin E, additional research is needed that involves human trials in order to determine if the outcomes that have been achieved largely in laboratory experiments can be recreated within the human body.
Introduction
Herbert M. Evans discovered vitamin E in his laboratory at the University of California, Berkley in 1922 (Packer, Weber & rimbach, 2001). Since that time, vitamin E has become one of the most researched compounds within the medical community because of the indication that one of more of the eight forms of vitamin E has properties that can effectively treat and even prevent the formation of cancer within the body (Moyad, Brumfield & Pienta, 1999; Aggarwal, Sundaram, Prasad & Kannappan, 2010). Gamma-tocopherol and tocotriencols in general are often discussed within the medical literature as providing the greatest opportunities for the reduction in cancer cells and the successful treatment of cancer (National Institutes of Health, 2011). These types of vitamin E have shown promise in treating a variety of cancers, including prostate cancer in men and breast cancer in women (Jordan, 2002). The purpose of this paper is to examine some of the existing research regarding the potential benefits of gamma-tocopherol and tocotriencols in relation to cancer treatment. Within this review of the literature, issues are discussed about how these forms of vitamin E may be effective at treating cancer, as well as areas in which further research is needed.
Vitamin E
Eight chemical forms of vitamin E have been found to exist, four of which are tocopherols and four of which are tocotrienols (National Institutes of Health, 2011). Research has shown that tocopherols and tocotrienols prevent the growth of cancer cells by causing apoptosis (Nesaretnam, Selvaduray, Razak, Veerasenan & Gomez, 2010). Of the two major types of vitamin E, tocopherols are more prevalent within the human body because they are the type of vitamin e that is most often obtained in people’s diets. In fact, alpha tocopherol is often the form of vitamin E that is referred to when researchers and nutritionists talk about vitamin E as a dietary supplement. Tocopherols are absorbed into cells through mucus in the intestine. Through the absorption process, tocopherols are transported to the liver through the lymphatic system where they are processed and their properties, which include the ability to reduce cancer cell growth, can occur (Ju, Picinich, Yang, Zhao, Suh, Kong & Yang, 2010).
However, it is tocotrienols that are more potent with regards to their ability to prevent the growth and spread of cancer cells because of their chemical makeup (Nesaretnam, Selvaduray, Razak, Veerasenan & Gomez, 2010). Unfortunately, while tocotrienols are found in fruits and vegetables, their levels are generally much lower than the levels of tocopherols that are obtained from eating these foods (Nesaretnam, Selvaduray, Razak, Veerasenan & Gomez, 2010). This means that in order to obtain the benefits related to the prevention and growth of cancer cells, tocotrienols must be injected into the body in ways other than through normal dietary processes.
It is important to note that simply taking large amounts of vitamin E, and particularly tocotrienols, is not something that should be done. First, research involving human trials has found an increased risk of stroke in relation to taking high doses of alpha tocopherol during cancer treatment (National Institutes of Health, 2011). Other research has found that the use of alpha tocopherol in cancer treatment does not inhibit the growth of cancer cells, which has been found to occur with the use of both gamma-tocopherol and tocotriencols (Jordan, 2002). Even beyond the problems that have been found involving the use of alpha tocopherol, other research has suggested that taking too much vitamin E can have pro-oxidant properties as opposed to anti-oxidant properties to reduce cancer cell formation (Brown, Morrice & Duthie, 1997). Taking too much vitamin E may actually create a set of conditions in the body that results in cancer cell formation occurring that would not have otherwise taken place. The warning that seems appropriate is that vitamin E at any dosage should not be viewed as a way of reducing the risk of cancer, or reducing cancer cells that have already formed. Even with the types of vitamin E that have shown great promise in the prevention and treatment of cancer, caution should be taken to ensure that too much vitamin E is not taken in the belief that any amount of the substance is beneficial.
Gamma-tocopherol and Cancer
Research has been undertaken to investigate the pro-apoptotic properties of gamma-tocopherol in relation to breast cancer cells (Yu, Park, Jia, Tiwary, Scott, Li, Wang, Simmons-Menchaca, Sanders & Klein, 2008). The research was undertaken using breast cancer cells in a laboratory setting, as opposed to breast cancer cells in humans. After injecting breast cancer cells with gamma-tocopherol, the breast cancer cells experienced apoptosis. However, the study also showed that non-cancerous cells did not undergo apoptosis when injected with gamma-tocopherol. The conclusion that was drawn from the findings of the study was that gamma-tocopherol may be effective at destroying breast cancer cells in humans through a process of activating the death receptor 5 pathway in mRNA.
A similar study was to determine if gamma-tocopherol caused apoptosis in colon cancer cells (Campbell, Stone, Lee, Whaley, Yang, Qui, Goforth, Sherman, McHaffie & Krishnan, 2006). The study was performed using a variety of colon cancer cell lines with differing genetic structures. By using colon cancer cell lines with different genetic structures, it was possible to determine the ability of gamma-tocopherol to cause apoptosis in colon cancer cells regardless of their genetic structures. The results of the study showed that gamma-tocopherol did cause significant amounts of apoptosis in colon cancer cells regardless of the generic structure of the cells. Interestingly, the study also tested the ability of alpha-tocopherol to cause apoptosis in colon cancer cell lines. The use of alpha-tocopherol actually did not cause apoptosis in the colon cancer cell lines. In the end, this study not only provided further evidence of the ability of gamma-tocopherol to induce apoptosis, but also the lack of strength in killing cancer cells on the part of alpha-tocopherol.
In addition to the ability of gamma-tocopherol to induce apoptosis in cancer cells, research has been conducted on the ability of gamma-tocopherol to increase the expression of PPAR, a nuclear receptor involved in the matabolism of fatty acid and cell proliferation (Campbell, Musich, Whaley, Stimmel, Leesnitzer, Dessus-Babus, duffourc, Stone, Newman, Yang, Krishnan, 2009). The study was conducted because of the correlation between consumption of dietary fat and chronic inflammation with an increase in prostate cancer. The results of the investigation confirmed that gamma-tocopherol did increase the PPAR pathway, which reduced fatty acid matabolism and the proliferation of colon cancer cells. Other research in this regard has further confirmed that gamma-tocopherol’s anti-inflammatory properties can reduce cell growth among cancer cells, but leave non-cancerous unaffected (Wiser, Alexis, Jiang, Wu, Robinette, roubey & Peden, 2008).
Overall, the research that has been reviewed has indicated that gamma-tocopherol has properties that allow it to induce apoptosis and reduce fatty acid metabolism in cancer cells while leaving non-cancerous cells unaffected. It is important to note, however, that the studies that have been reviewed were conducted in a laboratory environment. Further human trials are needed to determine if the outcomes achieved in the laboratory can be recreated in the human body.
Tocotrienols and Cancer
As compared to tocopherols, tocotriencols have been found to be much more potent in terms of the prevention and reproduction of cancerous cells in the body (Sylvester & Shah, 2005). Part of the reason that tocotriencols have been found to be better at preventing and reducing the reproduction of cancer cells in the body is because of greater cellular accumulation. Tocotriencols are more likely than tocopherols to achieve higher levels of accumulation at the cellular level. Because of the greater cellular accumulation that occurs on the part of tocotriencols as compared to gamma-tocopherol, the cell reproduction cycle may be inhibited at a higher rate as is possible with gamma-tocopherol. This means that cancer cells are not able to reproduce as rapidly as might otherwise occur.
In addition, research has been conducted to examine the impact of the cellular accumulation properties of of tocoriencols (Viola, Pilolli, Piroddi, Pierpaoli, Orlando, Provinciali, Betti, Mazzini & Galli, 2012). The results of the study revealed that the greater cellular accumulation of tocotriencols may cause an increase in mitochondrial toxicity and apoptosis, which results in the reduction of cancer cell reproduction where it has already begun, as well as the prevention of new cancer cells forming. The intake of tocotriencols may not only have the ability to reduce the reproduction of cancer cells, but also the ability to prevent the development of cancer cells by inhibiting the cell reproduction cycle.
Research has also been conducted to examine the way in which tocotrienols target the molecular structure of cancer cells as compared to gamma-tocopherols (Aggarwal, Sundaram, Prasad & Kannappan, 2010). The investigation showed that tocotriencols target different molecular structures than tocopherols in cancer cells. Specifically, the anti-inflammatory properties of tocotriencols were found to suppress the transcription factor NF-kB, which has been linked to tumorigensis and inhibition of HMG-CoA reductase, mammalian DNA polymerases, and some protein tyrosine kinesis.
Aside from the characteristics of tocotrienol that allow it to more effectively target cancer cells, research involving human trials have actually shown that tocotriencols have the ability to work in conjuection with standard cancer treatments (Nesaretnam, Meganathan, Veerasenan & Selvaduray, 2012). Specifically, Tamoxifen is the standard treatment in patients with estrogen receptor positive tumors in the breasts. The problem, however, is that most people develop a resistance to Tamoxifen. The findings of the study showed that a combination of tocotrienols and Tamoxifen have resulted in positive outcomes in treating breast cancer even after patients develop Tamoxifen resistance.
Overall, the research involving the use of tocotrienols in the treatment of cancer has showed that similar processes occur with regards to the way in which tocotrienols cause apoptosis in cancer cells as compared to gamma-tocopherol. However, the benefit of tocotrienols is that they accumulate at a higher level than gamma-tocopherol in cancer cells. This means that apoptosis of cancer cells occurs at a greater level, and that the prevention of the spread of cancer cells is stronger than with gamma-tocopherol.
Conclusion
The purpose of this paper has been to examine the use of Vitamin E in preventing cancer and stopping the spread of cancer cells. The research that was reviewed showed that both gamma-tocopherol and tocotrienols have been effective at inducing apoptosis in cancer cells. The research involving the use of gamma-tocopherol was found to be effective at inducing apoptosis in colon cancer cells regardless of their genetic structures. Even more, gamma-tocopherol has been found to indicate the death receptor in mRNA. However, the research suggests that tocotrienols may be more effective at inducing apoptosis in cancer cells because of a greater accumulation of this type of vitamin E at the cellular level. Furthermore, research has shown that in human trials of the treatment of breast cancer, tocotrienols can be used along with Tamoxifen to successfully stop the proliferation of breast cancer cells even after patients develop Tamoxifen resistance. Unfortunately, most of the research that has been conducted using gamma-tocopherols and tocotrienols have been conducted in the laboratory. More research involving human trials is needed in order to determine if the results achieved in the laboratory can be recreated in humans. Even more, care must be taken to inform the public that simply taking large doses of vitamin E is not likely to result in the successful prevention of treatment of cancer. This is due to the fact that most vitamin E that is consumed in dietary form is alpha-tocopherol, which has been shown to be ineffective at inducing apoptosis, and may even cause cancer cell proliferation.
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