Peripheral GABA Signaling Pathways: Novel Targets for Breast Cancer Therapy

Introduction: In addition to its role in adult mammalian nervous system as an inhibitory neurotransmitter, gammaaminobutyric acid (GABA) is involved in the proliferation, differentiation, and migration of cancer cells. Amongst these, breast cancer has been estimated as one of the most common types of cancer in women. GABA and its derivatives were shown to be effective in inhibition of many tumors including breast cancer. On the other hand its deficiency can be a primary cause of many types of malignancy. We hereby try to summarize the potential roles of GABA and its receptors in tumor progression and therapies in breast cancer. Methods and Materials:GABA is mostly referred to as a neurotransmitter, however, recently its existence in peripheral tissues is attracting the attentions, as increased expression of GABAB receptors has been detected in several human cancer cells and tissues. Hence, the antioncogenic signaling of GABA is discovered and therefore, by studying the full molecular interactions in peripheral GABA antioncogenic pathway it will be possible to find new targets for cancer therapy. These studies include the knowledge of structural and interaction properties of important GABA receptors in neoplastic tissues through experimental and in silico techniques. Results and discussion: Taken together, many GABA derivatives and GABA receptor agonists are proposed to use as cancer therapeutics and in many cases for breast cancer. The use of GABAergic agents as adjuvants to standard cancer therapy are also shown to have significant beneficial effects on the outcome of cancer by inhibiting the proliferation and migration. In addition, the regular intake of GABA as a dietary supplement may reduce incidence in individuals at a higher risk of neoplastic disease including breast cancer. Conclusions: By developing knowledge based strategies and using experimental and in silico implementations, peripheral GABA signaling pathways are a novel target in breast cancer-therapy.

کلیدواژه ها:

GABA ، signaling pathway ، Cancer therapy ، Breast cancer