Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Acid Ceramidase: A Novel Therapeutic Target in Cancer

Author(s): Yadu Vijayan, Manendra Babu Lankadasari and Kuzhuvelil B. Harikumar*

Volume 19, Issue 17, 2019

Page: [1512 - 1520] Pages: 9

DOI: 10.2174/1568026619666190227222930

Price: $65

Abstract

Sphingolipids are important constituents of the eukaryotic cell membrane which govern various signaling pathways related to different aspects of cell survival. Ceramide and Sphingosine are interconvertible sphingolipid metabolites, out of which Ceramide is pro-apoptotic and sphingosine is anti-apoptotic in nature. The conversion of ceramide to sphingosine is mediated by Acid Ceramidase (ASAH1) thus maintaining a rheostat between a tumor suppressor and a tumor promoter. This rheostat is completely altered in many tumors leading to uncontrolled proliferation. This intriguing property of ASAH1 can be used by cancer cells to their advantage, by increasing the expression of the tumor promoter, sphingosine inside cells, thus creating a favorable environment for cancer growth. The different possibilities through which this enzyme serves its role in formation, progression and resistance of different types of cancers will lead to the possibility of making Acid Ceramidase a promising drug target. This review discusses the current understanding of the role of acid ceramidase in cancer progression, metastasis and resistance, strategies to develop novel natural and synthetic inhibitors of ASAH1 and their usefulness in cancer therapy.

Keywords: Acid ceramidase, Sphingosine, Cancer, Metastasis, Chemotherapy, Radiation.

« Previous Next »
Graphical Abstract

[1]
Guan, X.L.; Souza, C.M.; Pichler, H.; Dewhurst, G.; Schaad, O.; Kajiwara, K.; Wakabayashi, H.; Ivanova, T.; Castillon, G.A.; Piccolis, M.; Abe, F.; Loewith, R.; Funato, K.; Wenk, M.R.; Riezman, H. Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Mol. Biol. Cell, 2009, 20(7), 2083-2095.
[http://dx.doi.org/10.1091/mbc.e08-11-1126] [PMID: 1922153]
[2]
Bienias, K.; Fiedorowicz, A.; Sadowska, A.; Prokopiuk, S.; Car, H. Regulation of sphingomyelin metabolism. Pharmacol. Rep., 2016, 68(3), 570-581.
[http://dx.doi.org/10.1016/j.pharep.2015.12.008] [PMID: 26940196]
[3]
Singh, P.; Li, R. Emerging roles for sphingolipids in cellular aging. Curr. Genet., 2018, 64(4), 761-767.
[http://dx.doi.org/10.1007/s00294-017-0799-z] [PMID: 29260307]
[4]
Hannun, Y.A.; Obeid, L.M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol., 2018, 19(3), 175-191.
[http://dx.doi.org/10.1038/nrm.2017.107] [PMID: 29165427]
[5]
Olsen, A.S.B.; Færgeman, N.J. Sphingolipids: membrane microdomains in brain development, function and neurological diseases. Open Biol., 2017, 7(5)170069
[http://dx.doi.org/10.1098/rsob.170069] [PMID: 28566300]
[6]
Molino, S.; Tate, E.; McKillop, W.M.; Medin, J.A. Sphingolipid pathway enzymes modulate cell fate and immune responses. Immunotherapy, 2017, 9(14), 1185-1198.
[http://dx.doi.org/10.2217/imt-2017-0089] [PMID: 29067886]
[7]
Maceyka, M.; Spiegel, S. Sphingolipid metabolites in inflammatory disease. Nature, 2014, 510(7503), 58-67.
[http://dx.doi.org/10.1038/nature13475] [PMID: 24899305]
[8]
Newton, J.; Lima, S.; Maceyka, M.; Spiegel, S. Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy. Exp. Cell Res., 2015, 333(2), 195-200.
[http://dx.doi.org/10.1016/j.yexcr.2015.02.025] [PMID: 25770011]
[9]
Mohammed, S.; Harikumar, K.B. Sphingosine 1-Phosphate: A novel target for lung disorders. Front. Immunol., 2017, 8, 296.
[http://dx.doi.org/10.3389/fimmu.2017.00296] [PMID: 28352271]
[10]
Liang, J.; Nagahashi, M.; Kim, E.Y.; Harikumar, K.B.; Yamada, A.; Huang, W.C.; Hait, N.C.; Allegood, J.C.; Price, M.M.; Avni, D.; Takabe, K.; Kordula, T.; Milstien, S.; Spiegel, S. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell, 2013, 23(1), 107-120.
[http://dx.doi.org/10.1016/j.ccr.2012.11.013] [PMID: 23273921]
[11]
Ogretmen, B. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer, 2018, 18(1), 33-50.
[http://dx.doi.org/10.1038/nrc.2017.96] [PMID: 29147025]
[12]
Wang, G.; Bieberich, E. Sphingolipids in neurodegeneration (with focus on ceramide and S1P). Adv. Biol. Regul., 2018, 70, 51-64.
[http://dx.doi.org/10.1016/j.jbior.2018.09.013] [PMID: 30287225]
[13]
Iqbal, J.; Walsh, M.T.; Hammad, S.M.; Hussain, M.M. Sphingolipids and lipoproteins in health and metabolic disorders. Trends Endocrinol. Metab., 2017, 28(7), 506-518.
[http://dx.doi.org/10.1016/j.tem.2017.03.005] [PMID: 28462811]
[14]
Lankadasari, M.B.; Aparna, J.S.; Mohammed, S.; James, S.; Aoki, K.; Binu, V.S.; Nair, S.; Harikumar, K.B. Targeting S1PR1/STAT3 loop abrogates desmoplasia and chemosensitizes pancreatic cancer to gemcitabine. Theranostics, 2018, 8(14), 3824-3840.
[http://dx.doi.org/10.7150/thno.25308] [PMID: 30083262]
[15]
Dai, L.; Liu, Y.; Xie, L.; Wu, X.; Qiu, L.; Di, W. Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis. Oncotarget, 2017, 8(43), 74947-74961.
[http://dx.doi.org/10.18632/oncotarget.20471] [PMID: 29088837]
[16]
Nagahashi, M.; Hait, N.C.; Maceyka, M.; Avni, D.; Takabe, K.; Milstien, S.; Spiegel, S. Sphingosine-1-phosphate in chronic intestinal inflammation and cancer. Adv. Biol. Regul., 2014, 54, 112-120.
[http://dx.doi.org/10.1016/j.jbior.2013.10.001] [PMID: 24210073]
[17]
Rodriguez, Y.I.; Campos, L.E.; Castro, M.G.; Aladhami, A.; Oskeritzian, C.A.; Alvarez, S.E. Sphingosine-1 Phosphate: A new modulator of immune plasticity in the tumor microenvironment. Front. Oncol., 2016, 6, 218.
[http://dx.doi.org/10.3389/fonc.2016.00218] [PMID: 27800303]
[18]
Coant, N.; Sakamoto, W.; Mao, C.; Hannun, Y.A. Ceramidases, roles in sphingolipid metabolism and in health and disease. Adv. Biol. Regul., 2017, 63, 122-131.
[http://dx.doi.org/10.1016/j.jbior.2016.10.002] [PMID: 27771292]
[19]
Kolesnick, R.N.; Goñi, F.M.; Alonso, A. Compartmentalization of ceramide signaling: Physical foundations and biological effects. J. Cell. Physiol., 2000, 184(3), 285-300.
[http://dx.doi.org/10.1002/1097-4652(20009)184:3<285:AID-JCP2>3.0.CO;2-3] [PMID: 10911359]
[20]
Jeckel, D.; Karrenbauer, A.; Birk, R.; Schmidt, R.R.; Wieland, F. Sphingomyelin is synthesized in the cis Golgi. FEBS Lett., 1990, 261(1), 155-157.
[http://dx.doi.org/10.1016/0014-5793(90)80659-7] [PMID: 2155131]
[21]
Bollinger, C.R.; Teichgräber, V.; Gulbins, E. Ceramide-enriched membrane domains. Biochim. Biophys. Acta, 2005, 1746(3), 284-294.
[http://dx.doi.org/10.1016/j.bbamcr.2005.09.001] [PMID: 16226325]
[22]
Zheng, W.; Kollmeyer, J.; Symolon, H.; Momin, A.; Munter, E.; Wang, E.; Kelly, S.; Allegood, J.C.; Liu, Y.; Peng, Q.; Ramaraju, H.; Sullards, M.C.; Cabot, M.; Merrill, A.H., Jr Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy. Biochim. Biophys. Acta, 2006, 1758(12), 1864-1884.
[http://dx.doi.org/10.1016/j.bbamem.2006.08.009] [PMID: 17052686]
[23]
Slotte, J.P. Biological functions of sphingomyelins. Prog. Lipid Res., 2013, 52(4), 424-437.
[http://dx.doi.org/10.1016/j.plipres.2013.05.001] [PMID: 23684760]
[24]
Koch, J.; Gärtner, S.; Li, C.M.; Quintern, L.E.; Bernardo, K.; Levran, O.; Schnabel, D.; Desnick, R.J.; Schuchman, E.H.; Sandhoff, K. Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification Of the first molecular lesion causing Farber disease. J. Biol. Chem., 1996, 271(51), 33110-33115.
[http://dx.doi.org/10.1074/jbc.271.51.33110] [PMID: 8955159]
[25]
Pei, J.; Grishin, N.V. Peptidase family U34 belongs to the superfamily of N-terminal nucleophile hydrolases. Protein Sci., 2003, 12(5), 1131-1135.
[http://dx.doi.org/10.1110/ps.0240803] [PMID: 12717035]
[26]
Bernardo, K.; Hurwitz, R.; Zenk, T.; Desnick, R.J.; Ferlinz, K.; Schuchman, E.H.; Sandhoff, K. Purification, characterization, and biosynthesis of human acid ceramidase. J. Biol. Chem., 1995, 270(19), 11098-11102.
[http://dx.doi.org/10.1074/jbc.270.19.11098] [PMID: 7744740]
[27]
Shtraizent, N.; Eliyahu, E.; Park, J.H.; He, X.; Shalgi, R.; Schuchman, E.H. Autoproteolytic cleavage and activation of human acid ceramidase. J. Biol. Chem., 2008, 283(17), 11253-11259.
[http://dx.doi.org/10.1074/jbc.M709166200] [PMID: 18281275]
[28]
Sugita, M.; Dulaney, J.T.; Moser, H.W. Ceramidase deficiency in Farber’s disease (lipogranulomatosis). Science, 1972, 178(4065), 1100-1102.
[http://dx.doi.org/10.1126/science.178.4065.1100] [PMID: 4678225]
[29]
Yu, F.P.S.; Amintas, S.; Levade, T.; Medin, J.A. Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J. Rare Dis., 2018, 13(1), 121.
[http://dx.doi.org/10.1186/s13023-018-0845-z] [PMID: 30029679]
[30]
Yu, F.P.S.; Sajdak, B.; Sikora, J.; Salmon, A.E.; Nagree, M.S.; Gurka, J.; Kassem, I.S.; Lipinski, D.M.; Carroll, J.; Medin, J.A. Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment. Am. J. Pathol., 2018.
[PMID: 30472209]
[31]
Azuma, N.; O’Brien, J.S.; Moser, H.W.; Kishimoto, Y. Stimulation of acid ceramidase activity by saposin D. Arch. Biochem. Biophys., 1994, 311(2), 354-357.
[http://dx.doi.org/10.1006/abbi.1994.1248] [PMID: 8203897]
[32]
He, X.; Okino, N.; Dhami, R.; Dagan, A.; Gatt, S.; Schulze, H.; Sandhoff, K.; Schuchman, E.H. Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase. J. Biol. Chem., 2003, 278(35), 32978-32986.
[http://dx.doi.org/10.1074/jbc.M301936200] [PMID: 12815059]
[33]
Gebai, A.; Gorelik, A.; Li, Z.; Illes, K.; Nagar, B. Structural basis for the activation of acid ceramidase. Nat. Commun., 2018, 9(1), 1621.
[http://dx.doi.org/10.1038/s41467-018-03844-2] [PMID: 29692406]
[34]
Bookstein, R.; Levy, A.; MacGrogan, D.; Lewis, T.B.; Weissenbach, J.; O’Connell, P.; Leach, R.J. Yeast artificial chromosome and radiation hybrid map of loci in chromosome band 8p22, a common region of allelic loss in multiple human cancers. Genomics, 1994, 24(2), 317-323.
[http://dx.doi.org/10.1006/geno.1994.1622] [PMID: 7698754]
[35]
Seelan, R.S.; Qian, C.; Yokomizo, A.; Bostwick, D.G.; Smith, D.I.; Liu, W. Human acid ceramidase is overexpressed but not mutated in prostate cancer. Genes Chromosomes Cancer, 2000, 29(2), 137-146.
[http://dx.doi.org/10.1002/1098-2264(2000)9999:9999<:AID-GCC1018>3.0.CO;2-E] [PMID: 10959093]
[36]
Mahdy, A.E.; Cheng, J.C.; Li, J.; Elojeimy, S.; Meacham, W.D.; Turner, L.S.; Bai, A.; Gault, C.R.; McPherson, A.S.; Garcia, N.; Beckham, T.H.; Saad, A.; Bielawska, A.; Bielawski, J.; Hannun, Y.A.; Keane, T.E.; Taha, M.I.; Hammouda, H.M.; Norris, J.S.; Liu, X. Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer. Mol. Ther., 2009, 17(3), 430-438.
[http://dx.doi.org/10.1038/mt.2008.281] [PMID: 19107118]
[37]
Camacho, L.; Meca-Cortés, O.; Abad, J.L.; García, S.; Rubio, N.; Díaz, A.; Celià-Terrassa, T.; Cingolani, F.; Bermudo, R.; Fernández, P.L.; Blanco, J.; Delgado, A.; Casas, J.; Fabriàs, G.; Thomson, T.M. Acid ceramidase as a therapeutic target in metastatic prostate cancer. J. Lipid Res., 2013, 54(5), 1207-1220.
[http://dx.doi.org/10.1194/jlr.M032375] [PMID: 23423838]
[38]
Samsel, L.; Zaidel, G.; Drumgoole, H.M.; Jelovac, D.; Drachenberg, C.; Rhee, J.G.; Brodie, A.M.; Bielawska, A.; Smyth, M.J. The ceramide analog, B13, induces apoptosis in prostate cancer cell lines and inhibits tumor growth in prostate cancer xenografts. Prostate, 2004, 58(4), 382-393.
[http://dx.doi.org/10.1002/pros.10350] [PMID: 14968439]
[39]
Holman, D.H.; Turner, L.S.; El-Zawahry, A.; Elojeimy, S.; Liu, X.; Bielawski, J.; Szulc, Z.M.; Norris, K.; Zeidan, Y.H.; Hannun, Y.A.; Bielawska, A.; Norris, J.S. Lysosomotropic acid ceramidase inhibitor induces apoptosis in prostate cancer cells. Cancer Chemother. Pharmacol., 2008, 61(2), 231-242.
[http://dx.doi.org/10.1007/s00280-007-0465-0] [PMID: 17429631]
[40]
Saad, A.F.; Meacham, W.D.; Bai, A.; Anelli, V.; Elojeimy, S.; Mahdy, A.E.; Turner, L.S.; Cheng, J.; Bielawska, A.; Bielawski, J.; Keane, T.E.; Obeid, L.M.; Hannun, Y.A.; Norris, J.S.; Liu, X. The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy. Cancer Biol. Ther., 2007, 6(9), 1455-1460.
[http://dx.doi.org/10.4161/cbt.6.9.4623] [PMID: 17881906]
[41]
Turner, L.S.; Cheng, J.C.; Beckham, T.H.; Keane, T.E.; Norris, J.S.; Liu, X. Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C6 ceramide. Prostate Cancer Prostatic Dis., 2011, 14(1), 30-37.
[http://dx.doi.org/10.1038/pcan.2010.47] [PMID: 21116286]
[42]
Cheng, J.C.; Bai, A.; Beckham, T.H.; Marrison, S.T.; Yount, C.L.; Young, K.; Lu, P.; Bartlett, A.M.; Wu, B.X.; Keane, B.J.; Armeson, K.E.; Marshall, D.T.; Keane, T.E.; Smith, M.T.; Jones, E.E.; Drake, R.R., Jr; Bielawska, A.; Norris, J.S.; Liu, X. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. J. Clin. Invest., 2013, 123(10), 4344-4358.
[http://dx.doi.org/10.1172/JCI64791] [PMID: 24091326]
[43]
Beckham, T.H.; Cheng, J.C.; Lu, P.; Marrison, S.T.; Norris, J.S.; Liu, X. Acid ceramidase promotes nuclear export of PTEN through sphingosine 1-phosphate mediated Akt signaling. PLoS One, 2013, 8(10)e76593
[http://dx.doi.org/10.1371/journal.pone.0076593] [PMID: 24098536]
[44]
Mizutani, N.; Inoue, M.; Omori, Y.; Ito, H.; Tamiya-Koizumi, K.; Takagi, A.; Kojima, T.; Nakamura, M.; Iwaki, S.; Nakatochi, M.; Suzuki, M.; Nozawa, Y.; Murate, T. Increased acid ceramidase expression depends on upregulation of androgen-dependent deubiquitinases, USP2, in a human prostate cancer cell line, LNCaP. J. Biochem., 2015, 158(4), 309-319.
[http://dx.doi.org/10.1093/jb/mvv039] [PMID: 25888580]
[45]
Romani, M.; Pistillo, M.P.; Banelli, B. Epigenetic targeting of glioblastoma. Front. Oncol., 2018, 8, 448.
[http://dx.doi.org/10.3389/fonc.2018.00448] [PMID: 30386738]
[46]
Abuhusain, H.J.; Matin, A.; Qiao, Q.; Shen, H.; Kain, N.; Day, B.W.; Stringer, B.W.; Daniels, B.; Laaksonen, M.A.; Teo, C.; McDonald, K.L.; Don, A.S. A metabolic shift favoring sphingosine 1-phosphate at the expense of ceramide controls glioblastoma angiogenesis. J. Biol. Chem., 2013, 288(52), 37355-37364.
[http://dx.doi.org/10.1074/jbc.M113.494740] [PMID: 24265321]
[47]
Realini, N.; Solorzano, C.; Pagliuca, C.; Pizzirani, D.; Armirotti, A.; Luciani, R.; Costi, M.P.; Bandiera, T.; Piomelli, D. Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity. Sci. Rep., 2013, 3, 1035.
[http://dx.doi.org/10.1038/srep01035] [PMID: 23301156]
[48]
Doan, N.B.; Alhajala, H.; Al-Gizawiy, M.M.; Mueller, W.M.; Rand, S.D.; Connelly, J.M.; Cochran, E.J.; Chitambar, C.R.; Clark, P.; Kuo, J.; Schmainda, K.M.; Mirza, S.P. Acid ceramidase and its inhibitors: a de novo drug target and a new class of drugs for killing glioblastoma cancer stem cells with high efficiency. Oncotarget, 2017, 8(68), 112662-112674.
[http://dx.doi.org/10.18632/oncotarget.22637] [PMID: 29348854]
[49]
Doan, N.B.; Nguyen, H.S.; Al-Gizawiy, M.M.; Mueller, W.M.; Sabbadini, R.A.; Rand, S.D.; Connelly, J.M.; Chitambar, C.R.; Schmainda, K.M.; Mirza, S.P. Acid ceramidase confers radioresistance to glioblastoma cells. Oncol. Rep., 2017, 38(4), 1932-1940.
[http://dx.doi.org/10.3892/or.2017.5855] [PMID: 28765947]
[50]
Pai, S.I.; Westra, W.H. Molecular pathology of head and neck cancer: implications for diagnosis, prognosis, and treatment. Annu. Rev. Pathol., 2009, 4, 49-70.
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092158] [PMID: 18729723]
[51]
Nema, R.; Vishwakarma, S.; Agarwal, R.; Panday, R.K.; Kumar, A. Emerging role of sphingosine-1-phosphate signaling in head and neck squamous cell carcinoma. OncoTargets Ther., 2016, 9, 3269-3280.
[PMID: 27330306]
[52]
Roh, J.L.; Park, J.Y.; Kim, E.H.; Jang, H.J. Targeting acid ceramidase sensitises head and neck cancer to cisplatin. Eur. J. Cancer, 2016, 52, 163-172.
[http://dx.doi.org/10.1016/j.ejca.2015.10.056] [PMID: 26687835]
[53]
Korbelik, M.; Banáth, J.; Zhang, W.; Saw, K.M.; Szulc, Z.M.; Bielawska, A.; Separovic, D. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine. Int. J. Cancer, 2016, 139(6), 1372-1378.
[http://dx.doi.org/10.1002/ijc.30171] [PMID: 27136745]
[54]
Klobučar, M.; Grbčić, P.; Pavelić, S.K.; Jonjić, N.; Visentin, S.; Sedić, M. Acid ceramidase inhibition sensitizes human colon cancer cells to oxaliplatin through downregulation of transglutaminase 2 and β1 integrin/FAK-mediated signalling. Biochem. Biophys. Res. Commun., 2018, 503(2), 843-848.
[http://dx.doi.org/10.1016/j.bbrc.2018.06.085] [PMID: 29920241]
[55]
Espaillat, M.P.; Snider, A.J.; Qiu, Z.; Channer, B.; Coant, N.; Schuchman, E.H.; Kew, R.R.; Sheridan, B.S.; Hannun, Y.A.; Obeid, L.M. Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment. FASEB J., 2018, 32(5), 2339-2353.
[http://dx.doi.org/10.1096/fj.201700585R] [PMID: 29259036]
[56]
Bowden, D.L.; Sutton, P.A.; Wall, M.A.; Jithesh, P.V.; Jenkins, R.E.; Palmer, D.H.; Goldring, C.E.; Parsons, J.L.; Park, B.K.; Kitteringham, N.R.; Vimalachandran, D. Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response. J. Proteomics, 2018, 179, 53-60.
[http://dx.doi.org/10.1016/j.jprot.2018.02.030] [PMID: 29518574]
[57]
Mishra, H.; Mishra, P.K.; Ekielski, A.; Jaggi, M.; Iqbal, Z.; Talegaonkar, S. Melanoma treatment: from conventional to nanotechnology. J. Cancer Res. Clin. Oncol., 2018, 144(12), 2283-2302.
[http://dx.doi.org/10.1007/s00432-018-2726-1] [PMID: 30094536]
[58]
Bedia, C.; Casas, J.; Andrieu-Abadie, N.; Fabriàs, G.; Levade, T. Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine. J. Biol. Chem., 2011, 286(32), 28200-28209.
[http://dx.doi.org/10.1074/jbc.M110.216382] [PMID: 21700700]
[59]
Lai, M.; Realini, N.; La Ferla, M.; Passalacqua, I.; Matteoli, G.; Ganesan, A.; Pistello, M.; Mazzanti, C.M.; Piomelli, D. Complete Acid Ceramidase ablation prevents cancer-initiating cell formation in melanoma cells. Sci. Rep., 2017, 7(1), 7411.
[http://dx.doi.org/10.1038/s41598-017-07606-w] [PMID: 28785021]
[60]
Liu, Y.; He, J.; Xie, X.; Su, G.; Teitz-Tennenbaum, S.; Sabel, M.S.; Lubman, D.M. Serum autoantibody profiling using a natural glycoprotein microarray for the prognosis of early melanoma. J. Proteome Res., 2010, 9(11), 6044-6051.
[http://dx.doi.org/10.1021/pr100856k] [PMID: 20879797]
[61]
Leclerc, J.; Garandeau, D.; Pandiani, C.; Gaudel, C.; Bille, K.; Nottet, N.; Garcia, V.; Colosetti, P.; Pagnotta, S.; Bahadoran, P.; Tondeur, G.; Mograbi, B.; Dalle, S.; Caramel, J.; Levade, T.; Ballotti, R.; Andrieu-Abadie, N.; Bertolotto, C. Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells. Oncogene, 2018.
[PMID: 30254208]
[62]
DeSantis, C.; Ma, J.; Bryan, L.; Jemal, A. Breast cancer statistics, 2013. CA Cancer J. Clin., 2014, 64(1), 52-62.
[http://dx.doi.org/10.3322/caac.21203] [PMID: 24114568]
[63]
Ruckhäberle, E.; Holtrich, U.; Engels, K.; Hanker, L.; Gätje, R.; Metzler, D.; Karn, T.; Kaufmann, M.; Rody, A. Acid ceramidase 1 expression correlates with a better prognosis in ER-positive breast cancer. Climacteric, 2009, 12(6), 502-513.
[http://dx.doi.org/10.3109/13697130902939913] [PMID: 19905902]
[64]
Sänger, N.; Ruckhäberle, E.; Györffy, B.; Engels, K.; Heinrich, T.; Fehm, T.; Graf, A.; Holtrich, U.; Becker, S.; Karn, T. Acid ceramidase is associated with an improved prognosis in both DCIS and invasive breast cancer. Mol. Oncol., 2015, 9(1), 58-67.
[http://dx.doi.org/10.1016/j.molonc.2014.07.016] [PMID: 25131496]
[65]
Morad, S.A.; Levin, J.C.; Tan, S.F.; Fox, T.E.; Feith, D.J.; Cabot, M.C. Novel off-target effect of tamoxifen--inhibition of acid ceramidase activity in cancer cells. Biochim. Biophys. Acta, 2013, 1831(12), 1657-1664.
[http://dx.doi.org/10.1016/j.bbalip.2013.07.016] [PMID: 23939396]
[66]
Bhabak, K.P.; Kleuser, B.; Huwiler, A.; Arenz, C. Effective inhibition of acid and neutral ceramidases by novel B-13 and LCL-464 analogues. Bioorg. Med. Chem., 2013, 21(4), 874-882.
[http://dx.doi.org/10.1016/j.bmc.2012.12.014] [PMID: 23312611]
[67]
Vethakanraj, H.S.; Babu, T.A.; Sudarsanan, G.B.; Duraisamy, P.K.; Ashok Kumar, S. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines. Biochem. Biophys. Res. Commun., 2015, 464(3), 833-839.
[http://dx.doi.org/10.1016/j.bbrc.2015.07.047] [PMID: 26188095]
[68]
Vethakanraj, H.S.; Sesurajan, B.P.; Padmanaban, V.P.; Jayaprakasam, M.; Murali, S.; Sekar, A.K. Anticancer effect of acid ceramidase inhibitor ceranib-2 in human breast cancer cell lines MCF-7, MDA MB-231 by the activation of SAPK/JNK, p38 MAPK apoptotic pathways, inhibition of the Akt pathway, downregulation of ERα. Anticancer Drugs, 2018, 29(1), 50-60.
[http://dx.doi.org/10.1097/CAD.0000000000000566] [PMID: 29023248]
[69]
Vejselova, D.; Kutlu, H.M.; Kuş, G. Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells. Cytotechnology, 2016, 68(6), 2721-2728.
[http://dx.doi.org/10.1007/s10616-016-9997-7] [PMID: 27380965]
[70]
Lucki, N.C.; Sewer, M.B. Genistein stimulates MCF-7 breast cancer cell growth by inducing acid ceramidase (ASAH1) gene expression. J. Biol. Chem., 2011, 286(22), 19399-19409.
[http://dx.doi.org/10.1074/jbc.M110.195826] [PMID: 21493710]
[71]
Ramírez de Molina, A.; de la Cueva, A.; Machado-Pinilla, R.; Rodriguez-Fanjul, V.; Gomez del Pulgar, T.; Cebrian, A.; Perona, R.; Lacal, J.C. Acid ceramidase as a chemotherapeutic target to overcome resistance to the antitumoral effect of choline kinase α inhibition. Curr. Cancer Drug Targets, 2012, 12(6), 617-624.
[http://dx.doi.org/10.2174/156800912801784811] [PMID: 22515519]
[72]
Yildiz-Ozer, M.; Oztopcu-Vatan, P.; Kus, G. The investigation of ceranib-2 on apoptosis and drug interaction with carboplatin in human non small cell lung cancer cells in vitro. Cytotechnology, 2018, 70(1), 387-396.
[http://dx.doi.org/10.1007/s10616-017-0154-8] [PMID: 29230631]
[73]
Morales, A.; París, R.; Villanueva, A.; Llacuna, L.; García-Ruiz, C.; Fernández-Checa, J.C. Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo. Oncogene, 2007, 26(6), 905-916.
[http://dx.doi.org/10.1038/sj.onc.1209834] [PMID: 16862171]
[74]
Tan, S.F.; Liu, X.; Fox, T.E.; Barth, B.M.; Sharma, A.; Turner, S.D.; Awwad, A.; Dewey, A.; Doi, K.; Spitzer, B.; Shah, M.V.; Morad, S.A.; Desai, D.; Amin, S.; Zhu, J.; Liao, J.; Yun, J.; Kester, M.; Claxton, D.F.; Wang, H.G.; Cabot, M.C.; Schuchman, E.H.; Levine, R.L.; Feith, D.J.; Loughran, T.P. Jr Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget, 2016, 7(50), 83208-83222.
[http://dx.doi.org/10.18632/oncotarget.13079] [PMID: 27825124]
[75]
Dementiev, A.; Joachimiak, A.; Nguyen, H.; Gorelik, A.; Illes, K.; Shabani, S.; Gelsomino, M.; Ahn, E.E.; Nagar, B.; Doan, N. Molecular mechanism of inhibition of acid ceramidase by carmofur. J. Med. Chem., 2018.
[PMID: 30525581]
[76]
Elojeimy, S.; Liu, X.; McKillop, J.C.; El-Zawahry, A.M.; Holman, D.H.; Cheng, J.Y.; Meacham, W.D.; Mahdy, A.E.; Saad, A.F.; Turner, L.S.; Cheng, J.A.; Day, T.; Dong, J.Y.; Bielawska, A.; Hannun, Y.A.; Norris, J.S. Role of acid ceramidase in resistance to FasL: therapeutic approaches based on acid ceramidase inhibitors and FasL gene therapy. Mol. Ther., 2007, 15(7), 1259-1263.
[http://dx.doi.org/10.1038/sj.mt.6300167] [PMID: 17426710]
[77]
Flowers, M.; Fabriás, G.; Delgado, A.; Casas, J.; Abad, J.L.; Cabot, M.C. C6-ceramide and targeted inhibition of acid ceramidase induce synergistic decreases in breast cancer cell growth. Breast Cancer Res. Treat., 2012, 133(2), 447-458.
[http://dx.doi.org/10.1007/s10549-011-1768-8] [PMID: 21935601]
[78]
Draper, J.M.; Xia, Z.; Smith, R.A.; Zhuang, Y.; Wang, W.; Smith, C.D. Discovery and evaluation of inhibitors of human ceramidase. Mol. Cancer Ther., 2011, 10(11), 2052-2061.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0365] [PMID: 21885864]
[79]
Eliyahu, E.; Shtraizent, N.; He, X.; Chen, D.; Shalgi, R.; Schuchman, E.H. Identification of cystatin SA as a novel inhibitor of acid ceramidase. J. Biol. Chem., 2011, 286(41), 35624-35633.
[http://dx.doi.org/10.1074/jbc.M111.260372] [PMID: 21846728]

Rights & Permissions Print Cite
Article Metrics
47
5
© 2024 Bentham Science Publishers | Privacy Policy