Cancer treatment contradiction - the double edge sword of Nitric Oxide

March 27, 2015

When laboratory scientific studies conflict with our body’s actual process of food constituents a double edge sword can occur. What and how the body handles organically occurring elements in food may be quite the opposite in vitro; hence contradictory evidence appears, leaving us wondering who is right.

Nitric Oxide otherwise known as NO is a molecule our own bodies produce. Within certain foods, like Beets, Garlic, Brown Rice, Cayenne Pepper, Peanuts, Pistachios, Walnuts, Watermelon, Oranges, Spinach, Kale, Onions, Pomegranates, and even honey, nitrates promote the production of nitric oxide, amino acids L-arginine and L-citrulline as well. Exercise increases the production of nitric oxide. With a proper amount of nitric oxide, it will act as a vasodilator relaxing arteries and allowing for good blood flow.

It is shown to improve memory, help the immune system fight bacteria and defend the body against tumors; it reduces inflammation and assists in the regulation of blood pressure. NO only lasts for a few seconds in the body so we need to eat the right foods to keep our production at a stable level.

Bacteria, viruses, parasites, and tissue inflammation in research have long been known to produce adverse changes in cells creating risk factors for a carcinogen effect on human cells. Nitric Oxide and other oxygen radicals are produced in infected and inflamed tissues, giving the reason for researchers to study the tissue type and DNA damage as a reactive result from the NO in these inflammatory processes; shedding light on the molecular mechanisms in chronic inflammatory conditions in humans.

Scientists are finding Nitric Oxide may contribute to angiogenesis [the production of new blood vessels] associated with the growth of tumors or metastases in patients with solid tumors, often in the head and neck. In an experiment tumor cells were implanted in rabbit corneas. They found higher levels of NO were found in tumor specimens that had lymph node involvement rather than those specimens from patients where there was no lymph involvement. Further studies showed in those specimens where NO activity was induced angiogenesis was present; where it was blocked, the tumor angiogenesis was repressed. Their conclusion is Nitric Oxide plays a role in tumor angiogenesis and tumor growth in neck and head cancers

Scientists and research studies in laboratories are showing Nitric Oxide’s role in various diseases are apparent. Yet, other studies show Nitric Oxide plays a role in inhibiting tumor growth. These contradictory studies have people wondering how good or how bad is Nitric Oxide. It is a double edge sword. On one side we see NO in certain stages of cancer promotes the growth of the tumors. Human breast cancer tumors, tumors of the nervous system, those in the head and neck as well as colon tumors are all found to have higher levels of NOs leading scientists to believe it is part of the mechanism for promoting tumor growth; yet in cancers that are of leukocyte origin NOs inhibit the cancer cell growth.

Cancer research is finding they can use Nitric Oxide depending on the type of cancer and the stage of cancer to work with certain chemotherapy or radiation treatments to enhance their activity. In vitro, it enhances the cytotoxic efficacy of these chemo agents as well as radiation. They have seen Nitric Oxide donors also have the ability to protect the body against chemotherapeutic agent damage. So we see Nitric Oxide plays a role in defense against cancer; with other reports suggesting it promotes tumor growth. This dichotomy largely depends on what stage NO is present; the quantities of NO production all demonstrate that factors such as timing, the concentration of NO, and location are needed to devise a strategy to utilize Nitric Oxide in clinical cancer treatments.

What we do know through laboratory research there exists a variety of mechanisms that allows NO to impact cancer development, stimulating it or repressing it; these effects of Nitric Oxide are broad and quite self – contradictory, showing cytotoxic processes while also suppressing tumor progression. We see tissues exposed to high levels of Nitric Oxide due to an inflammatory process or through exposure to environmental toxins could accumulate, causing mutation through direct NO excessive production or through potentiation of other genotoxic agents. In early stages the NO could also act as a natural killer; however, in further advanced stages, it will in turn mediate and support angiogenesis. In the correct concentration, you could see Nitric Oxide limits metastases causing apoptosis; the important consideration research is finding what and how Nitric Oxide plays a role in cancer treatment is timing and concentration.

While all the studies and research are being done in laboratories and scientists are debating how to measure concentration, when and how to use it to enhance chemotherapeutic effects and when to try to use it to protect against chemo agent damage or to try to use it to create apoptosis; other researchers are looking at Nitric Oxide in the body through the intake of food. What they are discovering is when it is utilized and obtained through food sources it enhances the immune system. Only when taken beyond moderate levels does the body show ill effects. Nitric Oxide is naturally produced in the body, usually thought, the increased production of NOs occurred through the synthesis of amino acids arginine and citrulline, it is now believed it can be generated from the digestion of dietary nitrates

Studies show in other countries where foods containing these nitrates and amino acids, as in colorful spices; there is a lower incidence of cancer. Consuming these foods lowers the risk of most chronic diseases, but these agents also are found to be also treating diseases through suppression of inflammatory pathways, proliferation of cancer cells, invasion, and angiogenesis of tumor cells. They conclude ingesting these foods offers diverse benefits. But gaining benefits of Nitric Oxide does not stop with Asian-derived spices. The potential of berries is related to the bioactive phytochemicals of colorful fruits as well. All these colorful foods and spices contain polyphenols, stilbenoids, lignans, and triterpenoids. They help reduce oxidative stress and inflammation. The berry bioactive regulates carcinogen and xenobiotic enzymes and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry fruit consumption may provide protection from chemotherapeutic agents.

Anthocyanins found in fruits and vegetables creating natural colors are shown to possess bioactive properties. Black rice was studied for this purpose and showed marked antioxidant activity and free radical scavenging capabilities in various in vitro research. Black rice extract reduced the formation of Nitric Oxide by suppressing inducible nitric oxide synthase expression in murine macrophage cells without cell toxicity. It showed the anthocyanin pigments had a marked amount of antioxidant and anti-inflammatory properties, giving cause to consider them as a potential nutraceutical formulation. Anthocyanins have strong inhibitory effects on Nitric Oxide production, berries, and other fruits, vegetables, and spices rich in anthocyanins extracts were reported through studies to significantly cause this effect. Red ginger and beetroot both of a red colorant were reported to suppress NO production so as to effectively affect acute and chronic inflammation and inhibit macrophage activation. The beets are filled with naturally occurring nitrates that convert into nitric oxide, thus it benefits oxygen and blood flow. So it can work to suppress overproduction as well as aid in a sufficient amount of conversion to aid the body.

The contradictory activities of Nitric Oxide can well be seen in how it reacts in vitro and how it reacts in the body through the conversion of food constituents into NOs. The timing and the amount of production are seen to be significant in how and what reaction it has on our bodies, pro, and con. When isolated and used in the body, as found in vitro studies, we see it can dramatically affect how a tumor effectively acts when given a chemotherapy agent enhanced with Nitric Oxide, and how it can adversely cause growth when given when a tumor is in an advanced stage in an inflammatory state. The assumption that nitric oxide is unstable may not be quite correct; this assumption comes from studying it within laboratory findings using nitric oxide donors. When studying the reactivity in that of nitric oxide itself in a natural production within the body through foods; suggests that the anti- angiogenesis potential in relevant food components could serve as a practical approach for the prevention and intervention of cancer.

Is it a double edge sword? As long as you keep within naturally occurring production of Nitric Oxide using food components the benefits are well reported; prevention is always better than being reactive.

Do you want to learn more about how to support your body to promote healing? Ask a staff member of Jesicha’s Hope on what beneficial options are available. You decide what is right for you. www.jesichashope.org Where education and hope meet to help you heal.

References:

http://www.nutritionexpress.com/showarticle.aspx?articleid=286

http://jnci.oxfordjournals.org/content/90/8/587.short

http://protein.bio.msu.ru/biokhimiya/contents/v63/full/63070948.html

http://www.sciencedirect.com/science/article/pii/0027510794902453

http://carcin.oxfordjournals.org/content/19/5/711.full.pdf+html

http://ebm.sagepub.com/content/234/8/825.short

http://online.liebertpub.com/doi/abs/10.1089/jmf.2009.1084

http://pubs.acs.org/doi/abs/10.1021/jf072504n

http://pubs.acs.org/doi/abs/10.1021/jf034466n

http://pubs.acs.org/doi/abs/10.1021/jf010976a

http://www.ncbi.nlm.nih.gov/pubmed/8944624

http://www.ncbi.nlm.nih.gov/pubmed/17691907