In March of 2016, a group of scientists in Baghdad released the results from a study they had conducted that tested the effects of nitric oxide for cancerous diseases. Their results were ground breaking in the health industry.
Nitric oxide (NO) is a volatile gas, which is produced in various areas of the body. It is a free radical, water soluble gas, which is practically present everywhere and plays an important role in several pathological and physiological processes. Over the past few years, scientists have been studying the effects of NO on tumor growth and carcinogenesis. However, its role in cancer biology is still not fully understood and there is considerable amount of confusion on how NO reacts with tumor cells.
Studies have shown that NO has both tumor promoting and tumoricidal effects, which depend on several factors such as its concentration, location, and timing. NO has properties which makes it a potential anti-oncogenic agent. On the other hand, it has also been observed to promote the initiation and modulation of several cancer-related events such as cell cycle, metastasis, invasion, apoptosis, and angiogenesis.
The members of nitric oxide synthesis (NOS) family are neuronal NOS (nNOS), endothelia (eNOS), and inducible NOS (iNOS), which are basically NO’s isoforms. Studies have shown that all these isoforms can be involved in slowing down or promoting the growth of cancer in the body. The activity of NOS expressions has been observed in several histogenetic origins and scientists have linked it with proliferation rate and tumor grade. You can read a full nitric oxide review here.
Nitric Oxide and Its Effects on Various Types of Cancer
It has been established from many studies that NO plays diverse roles in different types of cancer. Here, we will look at how nitric oxide reacts with different organs having tumors cells and whether it inhibits tumor growth or promotes it.
Cervical cancer is reported to cause more than 200,000 deaths annually and it is the second most common cancer found among women . This type of cancer is caused due to a dozen of risk factors including long-term use of oral contraceptives, smoking, chronic inflammation, multiparity, and other sexually transmitted infections (like herpes simplex virus type 2 and chlamydia trachomatis).
Studies have shown that these risk factors contribute to the increase in nitric oxide levels in the areas affected by cervical cancer. Moreover, markers of NO-mediated mutagenesis and increased levels of NO have been observed in females suffering from cervical intraepithelial neoplasia.
From these findings, it can be concluded that nitric oxide acts as a mutagenic agent and promotes carcinogenic activity in cervical cancer patients.
Breast cancer is the most common type of cancer found in women across the globe. Studies on the effect of nitric oxide on breast cancer indicate that it promotes the growth of tumor in the breast area. More specifically, it affects breast carcinoma cell lines and breast cancer tissues. In breast carcinomas, significant activity of NOS isoforms has been found as well as in situcarcinoma. Another study has reported higher NOS activity in invasive breast tumors and elevated amounts of nitric oxide have been observed in patients suffering from breast cancer .
From these findings, it can be concluded that NOS activity may be an early contributor of the carcinogenesis of breast cancer.
Lung cancer is mainly caused by tobacco smoke, as it leads to the buildup and activation of leukocytes because of chronic airway inflammation. This results in the production of high levels of nitric oxide and ROS. Various studies indicate that lung cancer patients have increased levels of nitrite, nitrotyrosine, and nitric oxide. Moreover, it has been found that smokers have considerably higher iNOS/NO levels than non-smokers. Lung cancer patients also have significant immunoreactivity for eNOS and iNOS in dysplastic lesions of their lungs. Another case study shows that some of the hexavalent chromium [Cr(VI)] compounds tend to promote pulmonary tumorigenesis.
From these findings, it can be concluded that an inflammatory environment in the lungs is formed when they are repeatedly exposed to particulate chromate, encompassed by high level of nitric oxide production, which ultimately leads to lung carcinogenesis.
Neurotransmission and vascular tone are some of the vital functions in which NO plays a key role. In several central nervous system disorders, NO has been seen to be the mediator of neurotoxicity. nNOS, one of the isoforms of NOS, may prove to be a supposedly useful indicator of the presence of brain tumor malignancy and differentiation.
A study focused on the examination of the effect of NADPH diaphorase and three NOS isoforms on brain tumor found that significant NOS activity was observed in malignant central nervous system neoplasms. It further concluded that the presence of NO may be related to pathophysiological processes, which are known to be important for brain tumor growth.
What can be Concluded?
NO is a free radical, relatively stable gas that tends to diffuse into cell membranes when it interacts with molecular targets and their cells. The nitric oxide reactions mostly depend on the subtle compositional variations of the extra- and intra-cellular settings and also on the concentration of NO. From the above findings, it can be seen that NO has a significant role in the initiation, development, and metastasis stages of various cancers and it has been observed that it plays a tumoricidal role as well.
Nitric oxide has both cytotoxic and cytostatic effect on tumor cells. However, most studies indicate that it plays protumoral instead of an antitumoral role once the carcinogenesis begins. It can also be said that low level activity of NOS expression promotes tumor growth, while high levels can have the opposite effect, i.e., it can act as cytotoxic or cytostatic for tumor cells.
Apart from these findings, NO has been found to have tumoricidal properties, which are utilized for cancer treatment. NO works as a sensitizer of tumor cells and enhances the effects of immunotherapy, chemotherapy, and radiotherapy in patients. However, to use NO for treatment purposes, further clinical trials and experimentation are required to elucidate the effects of nitric oxide on cancer prevention.