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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Mini-Review Article

Various Effects of the GABAergic System on Cancer: The Conditions and Specificities of its use in the Treatment of Some Cancers

Author(s): Hossein Tahmasebi Dehkordi, Sorayya Ghasemi* and Masoumeh Eliyasi Dashtaki

Volume 23, Issue 20, 2023

Published on: 22 May, 2023

Page: [1928 - 1936] Pages: 9

DOI: 10.2174/1568026623666230515163713

Price: $65

Open Access Journals Promotions 2
Abstract

GABA is an essential neurotransmitter in tissues other than the brain and has different functions. Cancer displays dysfunctional GABAergic system roles, comprising GAD, GABA, and GABA receptors. Both tumor-suppressing and carcinogenic characteristics of the GABAergic system have been reported in several malignancies. In the development of cancer cells, it plays oncogenesis- related roles. However, in some tumors, such as pancreatic cancer, it exhibits anti-cancer benefits in numerous human trials and animal models. As a result, GABAergic therapy may be used to treat cancer. The oxidative condition and the status of several malignant circumstances significantly influence the final GABAergic function in many tumors. Depending on the type of malignant tissue and other modifications, these roles manifest differently in malignancies. In this review, we, for the first time, concentrated on the oncogenic and tumor suppressor functions of GABA in various neoplasms, as well as its potential therapeutic implications. The significance of tumor suppressor function and the conditions that promote its function as a cancer genesis factor in cancer are discussed in this article.

Keywords: GABA, CNS, Tumor suppressor, Oncogene, GAD, GABAergic system.

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[1]
Gramazio, P.; Takayama, M.; Ezura, H. Challenges and prospects of new plant breeding techniques for GABA improvement in crops: Tomato as an example. Front. Plant Sci., 2020, 11, 577980.
[http://dx.doi.org/10.3389/fpls.2020.577980] [PMID: 33014001]
[2]
Ramos-Ruiz, R.; Poirot, E.; Flores-Mosquera, M. GABA, a non-protein amino acid ubiquitous in food matrices. Cogent Food Agric., 2018, 4(1), 1534323.
[http://dx.doi.org/10.1080/23311932.2018.1534323]
[3]
Ma, J.; Zhang, Y.; Wang, J.; Zhao, T.; Ji, P.; Song, J.; Zhang, H.; Luo, W. Proliferative effects of gamma-amino butyric acid on oral squamous cell carcinoma cells are associated with mitogen-activated protein kinase signaling pathways. Int. J. Mol. Med., 2016, 38(1), 305-311.
[http://dx.doi.org/10.3892/ijmm.2016.2597] [PMID: 27222045]
[4]
Al-Wadei, H.A.N.; Ullah, M.F.; Al-Wadei, M. GABA (γ-aminobutyric acid), a non-protein amino acid counters the β-adrenergic cascade-activated oncogenic signaling in pancreatic cancer: A review of experimental evidence. Mol. Nutr. Food Res., 2011, 55(12), 1745-1758.
[http://dx.doi.org/10.1002/mnfr.201100229] [PMID: 21805621]
[5]
Kim, K.H.; Kwon, Y.K.; Cho, C.K.; Lee, Y.W.; Lee, S.H.; Jang, S.G.; Yoo, B.C.; Yoo, H.S. Galectin-3-independent Down-regulation of GABABR1 due to treatment with korean herbal extract HAD-B reduces proliferation of human colon cancer cells. J. Pharmacopuncture, 2012, 15(3), 19-30.
[http://dx.doi.org/10.3831/KPI.2012.15.002] [PMID: 25780644]
[6]
Taylor, R.A.; Watt, M.J. Unsuspected protumorigenic signaling role for the oncometabolite GABA in advanced prostate cancer. Cancer Res., 2019, 79(18), 4580-4581.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-2182] [PMID: 31519776]
[7]
Ling, K.C.; Hagan, D.W.; Santini-González, J.; Phelps, E.A. Effects of sustained GABA releasing implants on pancreatic islets in mice. Drug Deliv. Transl. Res., 2021, 11(5), 2198-2208.
[http://dx.doi.org/10.1007/s13346-020-00886-2] [PMID: 33454926]
[8]
Dahn, M.L.; Walsh, H.R.; Dean, C.A.; Giacomantonio, M.A.; Fernando, W.; Murphy, J.P.; Walker, O.L.; Wasson, M.C.D.; Gujar, S.; Pinto, D.M.; Marcato, P. Metabolite profiling reveals a connection between aldehyde dehydrogenase 1A3 and GABA metabolism in breast cancer metastasis. Metabolomics, 2022, 18(1), 9.
[http://dx.doi.org/10.1007/s11306-021-01864-6] [PMID: 34989902]
[9]
Kanbara, K.; Otsuki, Y.; Watanabe, M.; Yokoe, S.; Mori, Y.; Asahi, M.; Neo, M. GABAB receptor regulates proliferation in the high-grade chondrosarcoma cell line OUMS-27 via apoptotic pathways. BMC Cancer, 2018, 18(1), 263.
[http://dx.doi.org/10.1186/s12885-018-4149-4] [PMID: 29514603]
[10]
Watanabe, M.; Maemura, K.; Oki, K.; Shiraishi, N.; Shibayama, Y.; Katsu, K. Gamma-Aminobutyric Acid (GABA) and cell proliferation: Focus on cancer cells. Histol. Histopathol., 2006, 21(10), 1135-1141.
[PMID: 16835836]
[11]
Watanabe, M.; Maemura, K.; Kanbara, K.; Tamayama, T.; Hayasaki, H. GABA and GABA receptors in the central nervous system and other organs. Int. Review Cytol., 2002, 213, 1-47.
[12]
Bhattacharya, D.; Gawali, V.S.; Kallay, L.; Toukam, D.K.; Koehler, A.; Stambrook, P.; Krummel, D.P.; Sengupta, S. Therapeutically leveraging GABA A receptors in cancer. Exp. Biol. Med. (Maywood), 2021, 246(19), 2128-2135.
[http://dx.doi.org/10.1177/15353702211032549] [PMID: 34649481]
[13]
Young, S.Z.; Bordey, A. GABA’s control of stem and cancer cell proliferation in adult neural and peripheral niches. Physiology (Bethesda), 2009, 24(3), 171-185.
[http://dx.doi.org/10.1152/physiol.00002.2009] [PMID: 19509127]
[14]
Brzozowska, A. Burdan, F.; Duma, D.; Solski, J.; Mazurkiewicz, M. γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer. Ann. Agric. Environ. Med., 2017, 24(3), 435-439.
[http://dx.doi.org/10.26444/aaem/75891] [PMID: 28954486]
[15]
Ngo, D.H.; Vo, T.S. An updated review on pharmaceutical properties of gamma-aminobutyric acid. Molecules, 2019, 24(15), 2678.
[http://dx.doi.org/10.3390/molecules24152678] [PMID: 31344785]
[16]
Huang, D.; Alexander, P.B.; Li, Q.J.; Wang, X.F. GABAergic signaling beyond synapses: an emerging target for cancer therapy. Trends Cell Biol., 2022, S0962-8924(22), 00195-7.
[http://dx.doi.org/10.1016/j.tcb.2022.08.004] [PMID: 36114091]
[17]
Du, Y.; Du, Z.; Zheng, H.; Wang, D.; Li, S.; Yan, Y.; Li, Y. GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells. Cell. Mol. Biol. Lett., 2013, 18(2), 149-162.
[http://dx.doi.org/10.2478/s11658-013-0081-4] [PMID: 23430456]
[18]
Ortega, A. A new role for GABA: inhibition of tumor cell migration. Trends Pharmacol. Sci., 2003, 24(4), 151-154.
[http://dx.doi.org/10.1016/S0165-6147(03)00052-X] [PMID: 12706998]
[19]
Solorzano, S.R.; Imaz-Rosshandler, I.; Camacho-Arroyo, I.; García-Tobilla, P.; Morales-Montor, G.; Salazar, P.; Arena-Ortiz, M.L.; Rodríguez-Dorantes, M. GABA promotes gastrin-releasing peptide secretion in NE/NE-like cells: Contribution to prostate cancer progression. Sci. Rep., 2018, 8(1), 10272.
[http://dx.doi.org/10.1038/s41598-018-28538-z] [PMID: 29980692]
[20]
Çiçek, S. Structure-dependent activity of natural GABA (A) receptor modulators. Molecules, 2018, 23(7), 1512.
[http://dx.doi.org/10.3390/molecules23071512] [PMID: 29932138]
[21]
Sieghart, W.; Sperk, G. Subunit composition, distribution and function of GABA (A) receptor subtypes. Curr. Top. Med. Chem., 2002, 2(8), 795-816.
[http://dx.doi.org/10.2174/1568026023393507] [PMID: 12171572]
[22]
Jiang, X.; Su, L.; Zhang, Q.; He, C.; Zhang, Z.; Yi, P.; Liu, J. GABAB receptor complex as a potential target for tumor therapy. J. Histochem. Cytochem., 2012, 60(4), 269-279.
[http://dx.doi.org/10.1369/0022155412438105] [PMID: 22266766]
[23]
Synowitz, M.; Ahmann, P.; Matyash, M.; Kuhn, S.A.; Hofmann, B.; Zimmer, C.; Kirchhoff, F.; Kiwit, J.C.W.; Kettenmann, H. GABA A -receptor expression in glioma cells is triggered by contact with neuronal cells. Eur. J. Neurosci., 2001, 14(8), 1294-1302.
[http://dx.doi.org/10.1046/j.0953-816x.2001.01764.x] [PMID: 11703458]
[24]
Johung, T.; Monje, M. Neuronal activity in the glioma microenvironment. Curr. Opin. Neurobiol., 2017, 47, 156-161.
[http://dx.doi.org/10.1016/j.conb.2017.10.009] [PMID: 29096244]
[25]
Zonouzi, M.; Scafidi, J.; Li, P.; McEllin, B.; Edwards, J.; Dupree, J.L.; Harvey, L.; Sun, D.; Hübner, C.A.; Cull-Candy, S.G.; Farrant, M.; Gallo, V. GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury. Nat. Neurosci., 2015, 18(5), 674-682.
[http://dx.doi.org/10.1038/nn.3990] [PMID: 25821912]
[26]
Samadani, U.; Judkins, A.R.; Akpalu, A.; Aronica, E.; Crino, P.B. Differential cellular gene expression in ganglioglioma. Epilepsia, 2007, 48(4), 646-653.
[http://dx.doi.org/10.1111/j.1528-1167.2007.00925.x] [PMID: 17437409]
[27]
Mindel, J.W.; Newton, H.B.; Moore, J.L. The neurophysiology of central nervous system tumors.In: Epilepsy and Brain Tumors; Newton, H.B.; Maschio, M., Eds.; Academic Press: Boston, 2015, pp. 119-132.
[http://dx.doi.org/10.1016/B978-0-12-417043-8.00008-0]
[28]
Chen, Z.A.; Bao, M.Y.; Xu, Y.F.; Zha, R.P.; Shi, H.B.; Chen, T.Y.; He, X.H. Suppression of human liver cancer cell migration and invasion via the GABAA receptor. Cancer Biol. Med., 2012, 9(2), 90-98.
[PMID: 23691461]
[29]
Minuk, G.Y. GABA and hepatocellular carcinoma. Mol. Cell. Biochem., 2000, 207(1/2), 105-108.
[http://dx.doi.org/10.1023/A:1007062802164] [PMID: 10888234]
[30]
Zhang, M.; Gong, Y.; Assy, N.; Minuk, G.Y. Increased GABAergic activity inhibits α-fetoprotein mRNA expression and the proliferative activity of the HepG2 human hepatocellular carcinoma cell line. J. Hepatol., 2000, 32(1), 85-91.
[http://dx.doi.org/10.1016/S0168-8278(00)80193-2] [PMID: 10673071]
[31]
Miao, Y.; Zhang, Y.; Wan, H.; Chen, L.; Wang, F. GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells. Biomed. Pharmacother., 2010, 64(9), 583-588.
[http://dx.doi.org/10.1016/j.biopha.2010.03.006] [PMID: 20888181]
[32]
Song, L. Du, A.; Xiong, Y.; Jiang, J.; Zhang, Y.; Tian, Z.; Yan, H. γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells. Tumour Biol., 2016, 37(11), 14885-14894.
[http://dx.doi.org/10.1007/s13277-016-5367-5] [PMID: 27644246]
[33]
An, J.; Seok, H.; Ha, E.M. GABA-producing Lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABAB receptor signaling. J. Microbiol., 2021, 59(2), 202-216.
[http://dx.doi.org/10.1007/s12275-021-0562-5] [PMID: 33527319]
[34]
Shaye, H.; Ishchenko, A.; Lam, J.H.; Han, G.W.; Xue, L.; Rondard, P.; Pin, J.P.; Katritch, V.; Gati, C.; Cherezov, V. Structural basis of the activation of a metabotropic GABA receptor. Nature, 2020, 584(7820), 298-303.
[http://dx.doi.org/10.1038/s41586-020-2408-4] [PMID: 32555460]
[35]
Schuller, H.M.; Al-Wadei, H.A.N.; Majidi, M. Gamma-amino-butyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma. Carcinogenesis, 2008, 29(10), 1979-1985.
[http://dx.doi.org/10.1093/carcin/bgn041] [PMID: 18310090]
[36]
Al-Wadei, H.A.N.; Plummer, H.K., III; Ullah, M.F.; Unger, B.; Brody, J.R.; Schuller, H.M. Social stress promotes and γ-aminobutyric acid inhibits tumor growth in mouse models of non-small cell lung cancer. Cancer Prev. Res. (Phila.), 2012, 5(2), 189-196.
[http://dx.doi.org/10.1158/1940-6207.CAPR-11-0177] [PMID: 21955519]
[37]
Schuller, H.M. Neurotransmitters and their receptors as the upstream regulators of the most common human cancers and their stem cells. J. Neurol. Neuromedicine, 2018, 3(6), 17-26.
[38]
Huang, Q.; Zhu, C.; Liu, C.; Xie, F.; Zhu, K.; Hu, S. Gamma-aminobutyric acid binds to GABAb receptor to inhibit cholangiocarcinoma cells growth via the JAK/STAT3 pathway. Dig. Dis. Sci., 2013, 58(3), 734-743.
[http://dx.doi.org/10.1007/s10620-012-2382-2] [PMID: 23007731]
[39]
Huang, Q.; Liu, C.; Wang, C.; Hu, Y.; Qiu, L.; Xu, P. Neurotransmitter γ-aminobutyric acid-mediated inhibition of the invasive ability of cholangiocarcinoma cells. Oncol. Lett., 2011, 2(3), 519-523.
[http://dx.doi.org/10.3892/ol.2011.263] [PMID: 22866114]
[40]
Tatsuta, M.; Iishi, H.; Baba, M.; Nakaizumi, A.; Ichii, M.; Taniguchi, H. Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Cancer Res., 1990, 50(16), 4931-4934.
[PMID: 2379157]
[41]
Al-Wadei, H.A.N.; Al-Wadei, M.H.; Ullah, M.F.; Schuller, H.M. Celecoxib and GABA cooperatively prevent the progression of pancreatic cancer in vitro and in xenograft models of stress-free and stress-exposed mice. PLoS One, 2012, 7(8), e43376.
[http://dx.doi.org/10.1371/journal.pone.0043376] [PMID: 22916251]
[42]
Razmkhah, F.; Soleimani, M.; Ghasemi, S.; Kafi-abad, S.A. MicroRNA-21 over expression in umbilical cord blood hematopoietic stem progenitor cells by leukemia microvesicles. Genet. Mol. Biol., 2019, 42(2), 465-471.
[http://dx.doi.org/10.1590/1678-4685-gmb-2018-0073] [PMID: 31429853]
[43]
Purwana, I.; Zheng, J.; Li, X.; Deurloo, M.; Son, D.O.; Zhang, Z.; Liang, C.; Shen, E.; Tadkase, A.; Feng, Z.P.; Li, Y.; Hasilo, C.; Paraskevas, S.; Bortell, R.; Greiner, D.L.; Atkinson, M.; Prud’homme, G.J.; Wang, Q. GABA promotes human β-cell proliferation and modulates glucose homeostasis. Diabetes, 2014, 63(12), 4197-4205.
[http://dx.doi.org/10.2337/db14-0153] [PMID: 25008178]
[44]
Untereiner, A.; Abdo, S.; Bhattacharjee, A.; Gohil, H.; Pourasgari, F.; Ibeh, N.; Lai, M.; Batchuluun, B.; Wong, A.; Khuu, N.; Liu, Y.; Rijjal, D.A.; Winegarden, N.; Virtanen, C.; Orser, B.A.; Cabrera, O.; Varga, G.; Rocheleau, J.; Dai, F.F.; Wheeler, M.B. GABA promotes β‐cell proliferation, but does not overcome impaired glucose homeostasis associated with diet‐induced obesity. FASEB J., 2019, 33(3), 3968-3984.
[http://dx.doi.org/10.1096/fj.201801397R] [PMID: 30509117]
[45]
Glassmeier, G.; Höpfner, M.; Buhr, H.; Lemmer, K.; Riecken, E.O.; Stein, H.; Quabbe, H.J.; Rancso, C.; Wiedenmann, B.; Scherübl, H. Expression of functional GABAA receptors in isolated human insulinoma cells. Ann. N. Y. Acad. Sci., 1998, 859(1 INTESTINAL PL), 241-248.
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb11138.x] [PMID: 9928397]
[46]
Takehara, A. Hosokawa, M.; Eguchi, H.; Ohigashi, H.; Ishikawa, O.; Nakamura, Y.; Nakagawa, H. γ-aminobutyric acid (GABA) stimulates pancreatic cancer growth through overexpressing GABAA receptor π subunit. Cancer Res., 2007, 67(20), 9704-9712.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2099] [PMID: 17942900]
[47]
Sizemore, G.M.; Sizemore, S.T.; Seachrist, D.D.; Keri, R.A. GABA(A) receptor pi (GABRP) stimulates basal-like breast cancer cell migration through activation of extracellular-regulated kinase 1/2 (ERK1/2). J. Biol. Chem., 2014, 289(35), 24102-24113.
[http://dx.doi.org/10.1074/jbc.M114.593582] [PMID: 25012653]
[48]
Ghasemi, S.; Mozdarani, H.; Soleimani, M. The Effect of miR-372 on genome instability in MKN-45 cell line. J. Isfahan Med. School, 2015, 32(311), 2035-2047.
[49]
Matuszek, M.; Jesipowicz, M.; Kleinrok, Z. GABA content and GAD activity in gastric cancer. Med. Sci. Monit., 2001, 7(3), 377-381.
[PMID: 11386012]
[50]
Maemura, K.; Shiraishi, N.; Sakagami, K.; Kawakami, K.; Inoue, T.; Murano, M.; Watanabe, M.; Otsuki, Y. Proliferative effects of γ-aminobutyric acid on the gastric cancer cell line are associated with extracellular signal-regulated kinase 1/2 activation. J. Gastroenterol. Hepatol., 2009, 24(4), 688-696.
[http://dx.doi.org/10.1111/j.1440-1746.2008.05687.x] [PMID: 19032445]
[51]
Wu, W.; Yang, Q.; Fung, K.M.; Humphreys, M.R.; Brame, L.S.; Cao, A.; Fang, Y.T.; Shih, P.T.; Kropp, B.P.; Lin, H.K. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer. Mol. Cell. Endocrinol., 2014, 383(1-2), 69-79.
[http://dx.doi.org/10.1016/j.mce.2013.11.017] [PMID: 24296312]
[52]
Azuma, H. Inamoto, T.; Sakamoto, T.; Kiyama, S.; Ubai, T.; Shinohara, Y.; Maemura, K.; Tsuji, M.; Segawa, N.; Masuda, H.; Takahara, K.; Katsuoka, Y.; Watanabe, M. γ-aminobutyric acid as a promoting factor of cancer metastasis; induction of matrix metalloproteinase production is potentially its underlying mechanism. Cancer Res., 2003, 63(23), 8090-8096.
[PMID: 14678958]
[53]
Huang, D.; Wang, Y.; Thompson, J.W.; Yin, T.; Alexander, P.B.; Qin, D.; Mudgal, P.; Wu, H.; Liang, Y.; Tan, L.; Pan, C.; Yuan, L.; Wan, Y.; Li, Q.J.; Wang, X.F. Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression. Nat. Cell Biol., 2022, 24(2), 230-241.
[http://dx.doi.org/10.1038/s41556-021-00820-9] [PMID: 35145222]
[54]
Jezewska, E.; Scinska, A.; Kukwa, W.; Sobolewska, A.; Turzynska, D.; Samochowiec, J.; Bienkowski, P. Gamma-aminobutyric acid concentrations in benign parotid tumours and unstimulated parotid saliva. J. Laryngol. Otol., 2011, 125(5), 492-496.
[http://dx.doi.org/10.1017/S0022215110002574] [PMID: 21205370]
[55]
Ghasemi, S.; Xu, S.; Nabavi, S.M.; Amirkhani, M.A.; Sureda, A.; Tejada, S.; Lorigooini, Z. Epigenetic targeting of cancer stem cells by polyphenols (cancer stem cells targeting). Phytother. Res., 2021, 35(7), 3649-3664.
[http://dx.doi.org/10.1002/ptr.7059] [PMID: 33619811]
[56]
Banerjee, J.; Papu John, A.M.S.; Al-Wadei, M.H.; Schuller, H.M. Prevention of pancreatic cancer in a hamster model by cAMP decrease. Oncotarget, 2016, 7(28), 44430-44441.
[http://dx.doi.org/10.18632/oncotarget.9790] [PMID: 27281617]
[57]
Al-Wadei, M.H.; Banerjee, J.; Al-Wadei, H.A.N.; Schuller, H.M. Nicotine induces self-renewal of pancreatic cancer stem cells via neurotransmitter-driven activation of sonic hedgehog signalling. Eur. J. Cancer, 2016, 52, 188-196.
[http://dx.doi.org/10.1016/j.ejca.2015.10.003] [PMID: 26689865]
[58]
Schuller, H.M. Regulatory Role of G Protein-coupled Receptors in Pancreatic Cancer Development and Progression. Curr. Med. Chem., 2018, 25(22), 2566-2575.
[http://dx.doi.org/10.2174/0929867324666170303121708] [PMID: 28260499]
[59]
Huang, H.Y.; Hsu, T.; Lin, B.F. Gamma-aminobutyric acid decreases macrophages infiltration and suppresses inflammatory responses in renal injury. J. Funct. Foods, 2019, 60, 103419.
[http://dx.doi.org/10.1016/j.jff.2019.103419]
[60]
Banerjee, J.; Papu John, A.M.; Al-Wadei, M.H.; Schuller, H.M. Abstract 823: Prevention of pancreatic cancer by cAMP control. Cancer Res., 2016, 76(14_Supplement Suppl.), 823-823.
[http://dx.doi.org/10.1158/1538-7445.AM2016-823]
[61]
Prud’homme, G.; Glinka, Y.; Wang, Q. GABA exerts anti-inflammatory and immunosuppressive effects (P5175). J. Immunol., 2013, 190(1), 68.
[62]
Greten, F.R.; Grivennikov, S.I. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity, 2019, 51(1), 27-41.
[http://dx.doi.org/10.1016/j.immuni.2019.06.025] [PMID: 31315034]
[63]
Zhang, S.; Zhao, J.; Hu, J.; He, H.; Wei, Y.; Ji, L.; Ma, X. Gama-Aminobutyric Acid (GABA) alleviates hepatic inflammation via GABA receptors/TLR4/NF-κB pathways in growing-finishing pigs generated by super-multiparous sows. Anim. Nutr., 2022, 9, 280-290.
[http://dx.doi.org/10.1016/j.aninu.2022.02.001] [PMID: 35600552]
[64]
Ogiwara, H.; Nordli, D.R.; DiPatri, A.J.; Alden, T.D.; Bowman, R.M.; Tomita, T. Pediatric epileptogenic gangliogliomas: seizure outcome and surgical results. J. Neurosurg. Pediatr., 2010, 5(3), 271-276.
[http://dx.doi.org/10.3171/2009.10.PEDS09372] [PMID: 20192644]
[65]
Smits, A.; Jin, Z.; Elsir, T.; Pedder, H.; Nistér, M.; Alafuzoff, I.; Dimberg, A.; Edqvist, P.H.; Pontén, F.; Aronica, E.; Birnir, B. GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. PLoS One, 2012, 7(5), e37041.
[http://dx.doi.org/10.1371/journal.pone.0037041] [PMID: 22615883]
[66]
Labrakakis, C.; Patt, S.; Hartmann, J.; Kettenmann, H. Functional GABA A receptors on human glioma cells. Eur. J. Neurosci., 1998, 10(1), 231-238.
[http://dx.doi.org/10.1046/j.1460-9568.1998.00036.x] [PMID: 9753131]
[67]
Schuller, H.M.; Al-Wadei, H.A. Beta-adrenergic signaling in the development and progression of pulmonary and pancreatic adenocarcinoma. Curr. Cancer Ther. Rev., 2012, 8(2), 116-127.
[http://dx.doi.org/10.2174/157339412800675351] [PMID: 23807873]
[68]
Schuller, H.; Al-Wadei, H.; Majidi, M. Inhibitory GABA signaling as a novel target for the prevention and therapy of pulmonary and pancreatic adenocarcinoma. Mol. Cancer Ther., 2007, 6(11)(Suppl.), B203-B203.
[69]
Schuller, H.M.; Al-Wadei, H.A.N.; Majidi, M. GABAB receptor is a novel drug target for pancreatic cancer. Cancer, 2008, 112(4), 767-778.
[http://dx.doi.org/10.1002/cncr.23231] [PMID: 18098271]
[70]
Fava, G. Marucci, L.; Glaser, S.; Francis, H.; De Morrow, S.; Benedetti, A.; Alvaro, D.; Venter, J.; Meininger, C.; Patel, T.; Taffetani, S.; Marzioni, M.; Summers, R.; Reichenbach, R.; Alpini, G. γ-Aminobutyric acid inhibits cholangiocarcinoma growth by cyclic AMP-dependent regulation of the protein kinase A/extracellular signal-regulated kinase 1/2 pathway. Cancer Res., 2005, 65(24), 11437-11446.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1470] [PMID: 16357152]
[71]
Sha, M.; Cao, J.; Sun, H.; Tong, Y.; Xia, Q. Neuroendocrine regulation of cholangiocarcinoma: A status quo review. Biochim. Biophys. Acta Rev. Cancer, 2019, 1872(1), 66-73.
[http://dx.doi.org/10.1016/j.bbcan.2019.05.005] [PMID: 31152820]
[72]
Thaker, P.H.; Yokoi, K.; Jennings, N.B.; Li, Y.; Rebhun, R.B.; Rousseau, D.L., Jr; Fan, D.; Sood, A.K. Inhibition of experimental colon cancer metastasis by the GABA-receptor agonist nembutal. Cancer Biol. Ther., 2005, 4(7), 753-758.
[http://dx.doi.org/10.4161/cbt.4.7.1827] [PMID: 15970706]
[73]
Liu, Y.; Li, Y.H.; Guo, F.J.; Wang, J.J.; Sun, R.L.; Hu, J.Y.; Li, G.C. Gamma-aminobutyric acid promotes human hepatocellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor α3 subunit. World J. Gastroenterol., 2008, 14(47), 7175-7182.
[http://dx.doi.org/10.3748/wjg.14.7175] [PMID: 19084931]
[74]
Wang, T.; Huang, W.; Chen, F. Baclofen, a GABAB receptor agonist, inhibits human hepatocellular carcinoma cell growth in vitro and in vivo. Life Sci., 2008, 82(9-10), 536-541.
[http://dx.doi.org/10.1016/j.lfs.2007.12.014] [PMID: 18222491]
[75]
Opolski, A.; Mazurkiewicz, M.; Wietrzyk, J.; Kleinrok, Z.; Radzikowski, C. The role of GABAergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer. J. Exp. Clin. Cancer Res., 2000, 19(3), 383-390.
[PMID: 11144533]
[76]
Abdul, M.; Mccray, S.D.; Hoosein, N.M. Expression of gamma-aminobutyric acid receptor (subtype A) in prostate cancer. Acta Oncol., 2008, 47(8), 1546-1550.
[http://dx.doi.org/10.1080/02841860801961265] [PMID: 18607852]
[77]
Sarasa, S.B.; Mahendran, R.; Muthusamy, G.; Thankappan, B.; Selta, D.R.F.; Angayarkanni, J. A Brief review on the non-protein amino acid, Gamma-Amino Butyric Acid (GABA): Its production and role in microbes. Curr. Microbiol., 2020, 77(4), 534-544.
[http://dx.doi.org/10.1007/s00284-019-01839-w] [PMID: 31844936]
[78]
Zhang, X. Du, Z.; Liu, J.; He, J. Γ -aminobutyric acid receptors affect the progression and migration of tumor cells. J. Recept. Signal Transduct. Res., 2014, 34(6), 431-439.
[http://dx.doi.org/10.3109/10799893.2013.856918] [PMID: 25167198]
[79]
Bhandage, A.K.; Barragan, A. GABAergic signaling by cells of the immune system: more the rule than the exception. Cell. Mol. Life Sci., 2021, 78(15), 5667-5679.
[http://dx.doi.org/10.1007/s00018-021-03881-z] [PMID: 34152447]
[80]
Cervantes-Villagrana, R.D.; Albores-García, D.; Cervantes-Villagrana, A.R.; García-Acevez, S.J. Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies. Signal Transduct. Target. Ther., 2020, 5(1), 99.
[http://dx.doi.org/10.1038/s41392-020-0205-z] [PMID: 32555170]
[81]
Inamoto, T.; Azuma, H.; Sakamoto, T.; Kiyama, S.; Ubai, T.; Kotake, Y.; Watanabe, M.; Katsuoka, Y. Invasive ability of human renal cell carcinoma cell line Caki-2 is accelerated by gamma-aminobutyric acid, via sustained activation of ERK1/2 inducible matrix metalloproteinases. Cancer Invest., 2007, 25(7), 574-583.
[http://dx.doi.org/10.1080/07357900701522471] [PMID: 18027151]
[82]
Huang, W.; Cao, L. Targeting GABA signalling for cancer treatment. Nat. Cell Biol., 2022, 24(2), 131-132.
[http://dx.doi.org/10.1038/s41556-021-00839-y] [PMID: 35145223]
[83]
Zhang, X.; Zhang, R.; Zheng, Y.; Shen, J.; Xiao, D.; Li, J.; Shi, X.; Huang, L.; Tang, H.; Liu, J.; He, J.; Zhang, H. Expression of gamma-aminobutyric acid receptors on neoplastic growth and prediction of prognosis in non-small cell lung cancer. J. Transl. Med., 2013, 11(1), 102.
[http://dx.doi.org/10.1186/1479-5876-11-102] [PMID: 23617850]
[84]
Motadi, L.; Moela, P. RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines. OncoTargets Ther., 2016, 9, 4721-4735.
[http://dx.doi.org/10.2147/OTT.S100964] [PMID: 27536134]
[85]
Huang, H.; Benzonana, L.L.; Zhao, H.; Watts, H.R.; Perry, N.J.S.; Bevan, C.; Brown, R.; Ma, D. Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination. Br. J. Cancer, 2014, 111(7), 1338-1349.
[http://dx.doi.org/10.1038/bjc.2014.426] [PMID: 25072260]
[86]
Tian, H.; Wu, J.X.; Shan, F.X.; Zhang, S.N.; Cheng, Q.; Zheng, J.N.; Pei, D.S. Gamma-aminobutyric acid induces tumor cells apoptosis via GABABR1•β-arrestins•JNKs signaling module. Cell Biochem. Biophys., 2015, 71(2), 679-688.
[http://dx.doi.org/10.1007/s12013-014-0247-3] [PMID: 25234615]
[87]
Lee, J.H.; Rho, S.B.; Chun, T. GABAA Receptor-Associated Protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47). Biotechnol. Lett., 2005, 27(9), 623-628.
[http://dx.doi.org/10.1007/s10529-005-3628-2] [PMID: 15977068]
[88]
Sung, H.Y.; Yang, S.D.; Ju, W.; Ahn, J.H. Aberrant epigenetic regulation of GABRP associates with aggressive phenotype of ovarian cancer. Exp. Mol. Med., 2017, 49(5), e335-e335.
[http://dx.doi.org/10.1038/emm.2017.62] [PMID: 28524180]

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