Role of amino acids neurotransmitters in cancer September 3, 2015 Latest Research Dopamine – an inexpensive drug currently used to treat heart, vascular and kidney disorders – can be safely used in cancer treatment to curb the growth of blood vessels in tumors. Reporting in the International Journal of Cancer, the researchers show that dopamine prevented the growth of blood vessels in two animal models without causing many of the serious side effects of the far-more expensive anti-angiogenic drugs currently used in cancer therapy. Furthermore, the agent prevented the drop in the number of neutrophils (i.e., neutropenia) found in the blood that is typically caused by 5-fluorouracil, a chemotherapy agent commonly used in the treatment of gastrointestinal and other tumors, such as colon, stomach, pancreas and breast cancers. In this study, researchers demonstrated for the first time that the inexpensive drug dopamine lacks the serious side toxicities commonly seen with the anti-angiogenesis drugs presently used in the clinic. Moreover, dopamine can prevent the low-neutrophil count that is often induced by a very common anti-cancer drug used for the treatment of gastrointestinal cancers. Also earlier studies have shown that dopamine blocks the growth of new blood vessels in tumors by inhibiting the action of vascular endothelial growth factor-A (VEGF-A). It is well-known that VEGF-A-induced angiogenesis plays a critical role in the initiation, growth and progression of solid tumors, and the majority of the anti-angiogenic drugs currently used in the clinics have anti-VEGF-A actions. These kind of studies will help to rapidly translate the use of this inexpensive but effective anti-angiogenic drug, dopamine, for the treatment of cancer in the clinics. From above mentioned studies we can come to some of conclusions: Dopamine did not cause hypertension or affect liver functions (i.e., levels of alanine aminotransferase and aspartate aminotransferase were not elevated, as can happen with currently available anti-VEGF drugs); Dopamine prevented neutropenia (low neutrophil count) induced by 5-FU, an anti-cancer drug commonly used to treat gastrointestinal cancers. Dopamine, in combination with anticancer drugs, significantly inhibited tumor growth and increased the life span when compared with treatment with dopamine or anticancer drugs alone. Dopamine had no direct effects on the growth and survival of tumor cells. The antiangiogenic action of dopamine was mediated by inhibiting proliferation and migration of tumor endothelial cells through suppression of VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation. On the other hand Epinephrine is known to elicit multiple systemic effects that include changes in cardiovascular parameters and immune responses. However, information about its direct action on cancer cells is limited. Recent evidences show that epinephrine reduces sensitivity of cancer cells to apoptosis through interaction with beta (2)-adrenergic receptors. The antiapoptotic mechanism of epinephrine primarily involves phosphorylation and inactivation of the proapoptotic protein BAD by cAMP-dependent protein kinase. Moreover, BAD phosphorylation was observed at epinephrine concentrations found after acute and chronic psychosocial stress. Antiapoptotic signaling by epinephrine could be one of the mechanisms by which stress promotes tumorigenesis and decreases the efficacy of anti-cancer therapies. This could mean that anxiolytic and beta blockers drugs may have anticancer properties and Beta -2 agonist may have tumorigenic effect. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate brain, participates outside the CNS in diverse functions such as platelet aggregation and the acrosomal reaction in spermatozoa. A recent study now demonstrates that GABA inhibits the migration of colon carcinoma (or prostate) cells and cancer growth, paving the way to the development of specific pharmacological agents that delay or inhibit invasion and metastasis of various cancer types. Glutamate is also among neurotransmitters that may affect tumorigenic process. Aberrant glutamatergic signaling (signaling involving glutamate) can lead to tumorigenesis and is likely the mechanism leading to many cancers. With a release of excess glutamate from cancer cells, nearby cells will either die or be transformed to participate in increased glutamatergic signaling through its increase in glutamate receptor expression. In this way, cancer cells invade normal tissues and transform normal cell signaling. Inflammation is mediated in part through glutamatergic signaling. At elevated levels, glutamate can initiate inflammation through activation of glial cells, a type of nerve cell. The glial cells then participate in cascading this glutamate stress signal throughout the body, particularly the brain, leading to chronic inflammation if glutamate levels remain elevated. Chronic inflammation leads to increased risk of cancer and a major underappreciated link is the role glutamate plays in these pathways. Finally glutamatergic pathway inhibitors may have tumorostatic (oncostatic) potential due to their role in cancer. References: http://cancer.osu.edu/news-and-media/news/study-suggests-that-dopamine-is-a-safe-anti-angiogenic-drug-in-cancer-treatment, http://www.ncbi.nlm.nih.gov/pubmed/18413843, http://www.dovepress.com/roles-of-dopamine-receptors-and-their-antagonist-thioridazine-in-hepat-peer-reviewed-article-OTT, http://www.ncbi.nlm.nih.gov/pubmed/17353197, http://www.psa-rising.com/med/mindbody/cancer-stress-epinephrine0407.htm, http://www.ncbi.nlm.nih.gov/pubmed/12706998, http://www.translational-medicine.com/content/11/1/102, http://jhc.sagepub.com/content/60/4/269.full, http://unblindmymind.org/2015/01/cancer-and-glutamate/, http://www.cancernetwork.com/prostate-cancer/glutamate-prostate-cancer-new-therapeutic-target-biomarker. Post Views: 2,120 Leave a Reply Cancel ReplyYou must be logged in to post a comment. This site uses Akismet to reduce spam. Learn how your comment data is processed.