Share This Article:

Expression of C-Terminal Modified Serine Palmitoyltransferase-1 Alters Chemosensitivity of Inflammation-Associated Human Cancer Cell Lines

Abstract Full-Text HTML Download Download as PDF (Size:3174KB) PP. 902-919
DOI: 10.4236/jct.2014.510097    1,612 Downloads   1,914 Views  
Author(s)    Leave a comment

ABSTRACT

Background: The human serine palmitoyltransferase-1, SPTLC1, subunit is emerging as a stress responsive protein with putative role in modulating cellular stress response behavior. When compared to the parental cell line, recombinant Glioma cells expressing C-terminal modified SPTLC1 are found to show resistance to the cytotoxic effect of polycyclic hydrocarbons, PHs, including the environmental contaminant 3-methylcholanthrene. This novel functional association of SPTLC1 expression with proliferative capacity is thought to be due, in part, to its ability for crosstalk with protein regulators of different biological processes. Whether the effect of SPTLC1 on sensitivity to PHs extends to therapeutic drugs and the progression of the malignant phenotype is of research interest. Methods: In the current study, sub-cellular localization was by immunostaining for SPTLC1 in untreated and chemical treated cells and detection with confocal microscopy. The effect expressing C-terminal modified SPTLC1, in cancer cell lines of the inflammation-associated type, has on chemosensitivity and gene expression was also assessed. Parent Glioma LN18 and SKN-SH cells and their SPTLC1 recombinants were each treated with Glutamate, an excitatory neurotransmitter that can participate in both neuronal and excitotoxic signaling. In addition to the Glioma and SKN-SH cells, the PC3 prostate cancer and 647V bladder cancer cell lines were also treated with Celecoxib, a potent inhibitor of cyclooxygenase 2, COX-2, and an anti-inflammatory drug recently found to have anti-neoplastic activity against several malignancies. Results: Confocal microscopy revealed that Celecoxib mediates both rapid and enhanced redistribution of SPTLC1 and COX-2, to focal adhesion sites. In cell viability assay, SPTLC1 recombinant cells exhibited differential but dose-dependent resistance to excitotoxic levels of Glutamate. Drug co-treatment with a non-lethal dose of the potent kinase inhibitor, Sulfasalazine, increased the anti-proliferation effect of Celecoxib in a dose-dependent manner for all the cell lines tested. Conclusions: The effect of SPTLC1 expression on cellular chemosensitivity seen in the present study further highlights possible role of a C-terminal modified SPTLC1 variant in the biologic modulation of cellular behavior in response to therapeutic anticancer drugs.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Yerokun, T. (2014) Expression of C-Terminal Modified Serine Palmitoyltransferase-1 Alters Chemosensitivity of Inflammation-Associated Human Cancer Cell Lines. Journal of Cancer Therapy, 5, 902-919. doi: 10.4236/jct.2014.510097.

References

[1] Yasuda, S. Nishijima, M. and Hanada, K. (2003) Localization, Topology and Function of the LCB1 Subunit of Serine Palmitoyltransferase in Mammalian Cells. The Journal of Biological Chemistry, 278, 4176-4183. http://dx.doi.org/10.1074/jbc.M209602200
[2] Dawkins, J.L., Hulme, D.J., Brahmbhatt, S.B., Auer-Grumbach, M. and Nicholson, G.A. (2001) Mutations in SPTLC1, Encoding Serine Palmitoyltransferase, Long Chain Base Subunit-1, Cause Hereditary Sensory Neuropathy Type I. Nature Genetics, 27, 309-312. http://dx.doi.org/10.1038/85879
[3] Wei, J. Yerokun, T., Leipelt, M., Haynes, C., Radhakrishna, H., Merrill, A.H., et al. (2009) Serine Palmitoyltransferase Subunit 1 Is Present in the Endoplasmic Reticulum, Nucleus and Focal Adhesions, and Functions in Cell Morphology. Biochimica et Biophysica Acta, 1791, 746-756. http://dx.doi.org/10.1016/j.bbalip.2009.03.016
[4] Carton, J.M., Uhlinger, D.J., Bartheja, A.D., Derian, C., Ho, G., Argenteri, D. and D’Andrea, M.R. (2003) Enhanced Serine Palmitoyltransferase Expression in Proliferating Fibroblasts, Transformed Cell Lines and Human Tumors. Journal of Histochemistry Cytochemistry, 51, 715-726.
http://dx.doi.org/10.1177/002215540305100603
[5] Bartheja, A.D., Uhlinger, D.J., Canton, J.M., Ho, G. and D’Andrea, M.R. (2003) Characterization of Serine Palmitoyltransferases in Normal Human Tissues. Journal of Histochemistry Cytochemistry, 51, 687-696. http://dx.doi.org/10.1177/002215540305100514
[6] Yerokun, T. and Stewart, J. (2006) Novel Functional Association of Serine Palmitoyltransferase 1—A Peptide in Sphingolipid Metabolism with Cytochrome p4501a1 Transactivation and Proliferative Capacity of the Human Glioma LN18 Brain Tumor Cell Line. International Journal of Environmental Research and Public Health, 3, 252-261. http://dx.doi.org/10.3390/ijerph2006030030
[7] Tamehiro, N., Zhou, S., Okuhira, K., Benita, Y., Brown, C.E., Zhuang, D.Z., Latz, E., Hornemann, T., von Eckardstein, A., Xavier, R.J., Freeman, M.W. and Fitzgerald, M.L. (2008) SPTLC1 Binds ABCA1 to Negatively Regulate Trafficking and Cholesterol Efflux Activity of the Transporter. Biochemistry, 47, 6138-6147. http://dx.doi.org/10.1021/bi800182t
[8] Penno, A., Reilly, M.M., Houlden, H., Laurá, M., Rentsch, K., Niederkofler, V., Stoeckli, E.T., Nicholson, G., Eichler, F., Brown Jr., R.H., von Eckardstein, A. and Hornemann, T. (2010) Hereditary Sensory Neuropathy Type 1 Is Caused by the Accumulation of Two Neurotoxic Sphingolipids. The Journal of Biological Chemistry, 285, 11178-11187. http://dx.doi.org/10.1074/jbc.M109.092973
[9] Dedov, V.N., Dedov, N. and Nicholson, G.A. (2004) Hypoxia Causes Aggregation of Serine Palmitoyltransferase Followed by Non-Apoptotic Death of Human Lymphocytes. Cell Cycle, 3, 1271-1277. http://dx.doi.org/10.4161/cc.3.10.1163
[10] Ravenna, L., Sale, P., Di Vito, M., Russo, A., Salvatori, L., Tafani, M., Mari, E., Sentinelli, S., Petrangeli, E., Gallucci, M., Di Silverio, F. and Russo, M.A. (2009) Up-Regulation of the Inflammatory-Reparative Phenotype in Human Prostate Carcinoma. Prostate, 69, 1245-1255.
http://dx.doi.org/10.1002/pros.20966
[11] Tafani, M., Russo, A., Di Vito, M., Sale, P., Pellegrini, L., Schito, L., Gentileschi, S., Bracaglia, R., Marandino, F., Garaci, E. and Russo, M.A. (2010) Up-Regulation of Proinflammatory Genes as Adaptation to Hypoxia in MCF-7 Cells and in Human Mammary Invasive Carcinoma Microenvironment. Cancer Science, 101, 1014-1023. http://dx.doi.org/10.1111/j.1349-7006.2010.01493.x
[12] Hornemann, T., Wei, Y. and von Eckardstein, A. (2007) Is the Mammalian Serine Palmitoyltransferase a High-Molecular-Mass Complex? Biochemical Journal, 405, 157-164.
[13] Ye, Z.C. and Sonteimer, H. (1999) Glioma Cells Release Excitotoxic Concentrations of Glutamate. Cancer Research, 59, 4383-4391.
[14] Takano, T., Lin, J.H., Arcuino, G., Gao, Q., Yang, J. and Nedergaard, M. (2001) Glutamate Release Promotes Growth of Malignant Gliomas. Nature Medicine, 7, 1010-1015.
http://dx.doi.org/10.1038/nm0901-1010
[15] Shih, A.Y., Erb, H., Sun, X., Toda, S., Kalivas, P.W. and Murphy, T.H. (2006) Cystine/Glutamate Exchange Modulates Glutathione Supply for Neuroprotection from Oxidative Stress and Cell Proliferation. The Journal of Neuroscience, 26, 10514-10523.
http://dx.doi.org/10.1523/JNEUROSCI.3178-06.2006
[16] Sonnewald, U., Qu, H. and Aschner, M. (2002) Pharmacology and Toxicology of Astrocyte-Neuron Glutamate Transport and Cycling. Journal of Pharmacology and Experimental Therapeutics, 301, 1-6. http://dx.doi.org/10.1124/jpet.301.1.1
[17] Bridges, R.J., Natale, N.R. and Patel, S.A. (2012) System xc-Cystine/Glutamate Antiporter: An Update on Molecular Pharmacology and Roles within the CNS. British Journal of Pharmacology, 165, 20-34. http://dx.doi.org/10.1111/j.1476-5381.2011.01480.x
[18] Murphy, T.H., Miyamoto, M., Sastre, A., Schnaar, R.L. and Coyle, J.T. (1989) Glutamate Toxicity in a Neuronal Cell Line Involves Inhibition of Cystine Transport Leading to Oxidative Stress. Neuron, 2, 1547-1558. http://dx.doi.org/10.1016/0896-6273(89)90043-3
[19] Praticò, D. (2002) Alzheimer’s Disease and Oxygen Radicals: New Insights. Biochemical Pharmacology, 63, 563-567. http://dx.doi.org/10.1016/S0006-2952(01)00919-4
[20] Huang, Y., Dai, Z., Barbacioru, C. and Sadée, W. (2005) Cystine-Glutamate Transporter SLC7A11 in Cancer Chemosensitivity and Chemoresistance. Cancer Research, 65, 7446-7454.
http://dx.doi.org/10.1158/0008-5472.CAN-04-4267
[21] Joki, T., Heese, O., Nikas, D.C., Bello, L., Zhang, J., Kraeft, S.K., Seyfried, N.T., Abe, T., Chen, L.B., Carroll, R.S. and Black, P.M. (2000) Expression of Cyclooxygenase 2 (COX-2) in Human Glioma and in Vitro Inhibition by a Specific COX-2 Inhibitor, NS-398. Cancer Research, 60, 4926-4931.
[22] Deininger, M.H., Weller, M., Streffer, J., Mittelbronn, M. and Meyermann, R. (1999) Patterns of Cyclooxygenase-1 and -2 Expression in Human Gliomas in Vivo. Acta Neuropathologica, 98, 240-244. http://dx.doi.org/10.1007/s004010051075
[23] Panagopoulos, A.T., Lancellotti, C.L., Veiga, J.C., de Aguiar, P.H. and Colquhoun, A. (2008) Expression of Cell Adhesion Proteins and Proteins Related to Angiogenesis and Fatty Acid Metabolism in Benign, Atypical, and Anaplastic Meningiomas. Journal of Neuro-Oncology, 89, 73-87.
http://dx.doi.org/10.1007/s11060-008-9588-3
[24] Annabi, B., Laflamme, C., Sina, A., Lachambre, M.P. and Béliveau, R. (2009) A MT1-MMP/NF-κB Signaling axis as a Checkpoint Controller of COX-2 Expression in CD133(+) U87 Glioblastoma Cells. Journal of Neuroinflammation, 6, 8. http://dx.doi.org/10.1186/1742-2094-6-8
[25] Ravenna, L., Sale, P., Di Vito, M., Russo, A., Salvatori, L., Tafani, M., Mari, E., Sentinelli, S., Petrangeli, E., Gallucci, M., Di Silverio, F. and Russo, M.A. (2009) Up-Regulation of the Inflammatory-Reparative Phenotype in Human Prostate Carcinoma. Prostate, 69, 1245-1255.
http://dx.doi.org/10.1002/pros.20966
[26] Arber, N., Eagle, C.J., Spicak, J., Rácz, I., Dite, P., Hajer, J., et al. (2006) Celecoxib for the Prevention of Colorectal Adenomatous Polyps. The New England Journal of Medicine, 355, 885-895. http://dx.doi.org/10.1056/NEJMoa061652
[27] Davies, N.M., McLachlan, A.J., Day, R.O. and Williams, K.M. (2000) Clinical Pharmacokinetics and Pharmacodynamics of Celecoxib: A Selective Cyclo-Oxygenase-2 Inhibitor. Clinical Pharmacokinetics, 38, 225-242. http://dx.doi.org/10.2165/00003088-200038030-00003
[28] Zhu, J., Huang, J.W., Tseng, P.H., Yang, Y.T., Fowble, J., Shiau, C.W., Shaw, Y.J., Kulp, S.K. and Chen, C.S. (2004) From the Cyclooxygenase-2 Inhibitor Celecoxib to a Novel Class of 3-Phosphoinositide-Dependent Protein Kinase-1 Inhibitors. Cancer Research, 64, 4309-4318.
http://dx.doi.org/10.1158/0008-5472.CAN-03-4063
[29] Tang, C., Shou, M., Rushmore, T.H., Mei, Q., Sandhu, P., Woolf, E.J., Rose, M.J., et al. (2001) In-Vitro Metabolism of Celecoxib, a Cyclooxygenase-2 Inhibitor, by Allelic Variant Forms of Human Liver Microsomal Cytochrome P450 2C9: Correlation with CYP2C9 Genotype and in-Vivo Pharmacokinetics. Pharmacogenetics, 11, 223-235.
[30] Ma, H.I., Chiou, S.H., Hueng, D.Y., Tai, L.K., Huang, P.I., Kao, C.L., Chen, Y.W. and Sytwu, H.K. (2011) Celecoxib and Radioresistant Glioblastoma-Derived CD133+ Cells: Improvement in Radiotherapeutic Effects. Journal of Neurosurgery, 114, 651-662. http://dx.doi.org/10.3171/2009.11.JNS091396
[31] Miller, T.W., Rexer, B.N., Garrett, J.T. and Arteaga, C.L. (2011) Mutations in the Phosphatidylinositol 3-Kinase Pathway: Role in Tumor Progression and Therapeutic Implications in Breast Cancer. Breast Cancer Research, 13, 224. http://dx.doi.org/10.1186/bcr3039
[32] Perroud, H.A., Rico, M.J., Alasino, C.M., Queralt, F., Mainetti, L.E., Pezzotto, S.M., Rozados, V.R. and Scharovsky, O.G. (2013) Safety and Therapeutic Effect of Metronomic Chemotherapy with Cyclophosphamide and Celecoxib in Advanced Breast Cancer Patients. Future Oncology, 9, 451-462. http://dx.doi.org/10.2217/fon.12.196
[33] Katkoori, V.R., Manne, K., Vital-Reyes, V.S., Rodríguez-Burford, C., Shanmugam, C., Sthanam, M., Manne, U., Chatla, C., Abdulkadir, S.A. and Grizzle, W.E. (2013) Selective COX-2 Inhibitor (Celecoxib) Decreases Cellular Growth in Prostate Cancer Cell Lines Independent of p53. Biotechnic & Histochemistry, 88, 38-46. http://dx.doi.org/10.3109/10520295.2012.724713
[34] James, N.D., Sydes, M.R., Mason, M.D., Clarke, N.W., Anderson, J., Dearnaley, D.P., et al. (2012) Celecoxib Plus Hormone Therapy versus Hormone Therapy Alone for Hormone-Sensitive Prostate Cancer: First Results from the STAMPEDE Multiarm, Multistage, Randomized Controlled Trial. The Lancet Oncology, 13, 549-558. http://dx.doi.org/10.1016/S1470-2045(12)70088-8
[35] Paulson, S.K., Hribar, J.D., Liu, N.W., Hajdu, E., Bible Jr., R.H., Piergies, A. and Karim, A. (2000) Metabolism and Excretion of [(14)C]Celecoxib in Healthy Male Volunteers. Drug Metab Dispos., 28, 308-314.
[36] Sandberg, M., Yasar, ü., Stromberg, P., Hoog, J.O. and Eliasson, E. (2002) Oxidation of Celecoxib by Polymorphic Cytochrome P450 2C9 and Alcohol Dehydrogenase. British Journal of Clinical Pharmacology, 54, 423-429. http://dx.doi.org/10.1046/j.1365-2125.2002.01660.x
[37] Rodrigues, A.D. (2005) Impact of CYP2C9 Genotype on Pharmacokinetics: Are All Cyclooxygenase Inhibitors the Same? Drug Metabolism and Disposition, 33, 1567-1575.
http://dx.doi.org/10.1124/dmd.105.006452
[38] Vasquez, H.G. and Strobel, H. (1998) Identification of Cytochrome P450s in Human Glioma Cell Line. International Journal of Oncology, 12, 1291-1294.
[39] Denison, M.S. and Whitlock Jr., J.P. (1995) Xenobiotic-Inducible Transcription of Cytochrome P450 Genes. Journal of Biological Chemistry, 270, 18175-18178.
http://dx.doi.org/10.1074/jbc.270.31.18175
[40] Guo, W., Reigan, P., Siegel, D. and Ross, D. (2008) Enzymatic Reduction and Glutathione Conjugation of Benzoquinone Ansamycin Heat Shock Protein 90 Inhibitors: Relevance for Toxicity and Mechanism of Action. Drug Metabolism and Disposition, 36, 2050-2057.
http://dx.doi.org/10.1124/dmd.108.022004
[41] Nebert, D.W., Wikvall, K. and Miller, W.L. (2013) Human Cytochromes P450 in Health and Disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 368, Article ID: 20120431. http://dx.doi.org/10.1098/rstb.2012.0431
[42] Guengerich, F.P. (1991) Molecular Advances for the Cytochrome P-450 Superfamily. Trends in Pharmacological Sciences, 12, 281-283. http://dx.doi.org/10.1016/0165-6147(91)90574-C
[43] Young, J.C., Barral, J.M. and Hartl, F.U. (2003) More than Binding: Localized Functions of Cytosolic Chaperones. Trends in Biochemical Sciences, 28, 541-547.
http://dx.doi.org/10.1016/j.tibs.2003.08.009
[44] Merrill Jr., A.H., Nikolova-Karakashian, M., Schmelz, E.M., Morgan, E.T. and Stewart, J. (1999) Regulation of Cytochrome P450 Expression by Sphingolipids. Chemistry and Physics of Lipids, 102, 131-139. http://dx.doi.org/10.1016/S0009-3084(99)00081-X
[45] Lin, H.P., Kulp, S.K., Tseng, P.H., Yang, Y.T., Yang, C.C. and Chen, C.S. (2004) Growth Inhibitory Effects of Celecoxib in Human Umbilical Vein Endothelial Cells Are Mediated through G1 Arrest via Multiple Signaling Mechanisms. Molecular Cancer Therapeutics, 3, 1671-1680.
[46] Zhang, G.S., Liu, D.S., Dai, C.W. and Li, R.J. (2006) Antitumor Effects of Celecoxib on K562 Leukemia Cells Are Mediated by Cell-Cycle Arrest, Caspase-3 Activation, and Downregulation of Cox-2 Expression and Are Synergistic with Hydroxyurea or Imatinib. American Journal of Hematology, 81, 242-255. http://dx.doi.org/10.1002/ajh.20542
[47] Gr?sch, S., Maier, T.J., Schiffmann, S. and Geisslinger, G. (2006) Cyclooxygenase-2 (COX-2)-Independent Anticarcinogenic Effects of Selective COX-2 Inhibitors. Journal of the National Cancer Institute, 98, 736-747. http://dx.doi.org/10.1093/jnci/djj206
[48] Kang, K.B., Zhu, C., Yong, S.K., Gao, Q. and Wong, M.C. (2009) Enhanced Sensitivity of Celecoxib in Human Glioblastoma Cells: Induction of DNA Damage Leading to p53-Dependent G1 Cell Cycle Arrest and Autophagy. Molecular Cancer, 8, 66. http://dx.doi.org/10.1186/1476-4598-8-66
[49] Lin, M.T., Lee, R.C., Yang, P.C., Ho, F.M. and Kuo, M.L. (2001) Cyclooxygenase-2 Inducing Mcl-1-Dependent Survival Mechanism in Human Lung Adenocarcinoma CL1.0 Cells. Involvement of Phosphatidylinositol 3-Kinase/Akt Pathway. The Journal of Biological Chemistry, 276, 8997-9002. http://dx.doi.org/10.1074/jbc.M107829200
[50] Ki, K., Gerelchuluun, A., Hong, Z., Sun, L., Zenkoh, J., Moritake, T. and Tsuboi, K. (2013) Celecoxib Enhances Radiosensitivity of Hypoxic Glioblastoma Cells through Endoplasmic Reticulum Stress. Neuro-Oncology, 15, 1186-1199.
[51] Balza, E., Castellani, P., Delfino, L., Truini, M. and Rubartelli, A. (2013) The Pharmacologic Inhibition of the xc-Antioxidant System Improves the Antitumor Efficacy of COX Inhibitors in the in Vivo Model of 3-MCA Tumorigenesis. Carcinogenesis, 34, 620-626. http://dx.doi.org/10.1093/carcin/bgs360
[52] Nabeyama, A., Kurita, A., Asano, K., Miyake, Y., Yasuda, T., Miura, I., Nishitai, G., Arakawa, S., Shimizu, S., Wakana, S., Yoshida, H. and Tanaka, M. (2010) xCT Deficiency Accelerates Chemically Induced Tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 107, 6436-6441. http://dx.doi.org/10.1073/pnas.0912827107
[53] Gout, P.W., Buckley, A.R., Simms, C.R. and Bruchovsky, N. (2001) Sulfasalazine, a Potent Suppressor of Lymphoma Growth by Inhibition of the xc-Cystine Transporter: A New Action for an Old Drug. Leukemia, 15, 1633-1640. http://dx.doi.org/10.1038/sj.leu.2402238
[54] de Groot, J. and Sontheimer, H. (2011) Glutamate and the Biology of Gliomas. Glia, 59, 1181-1189. http://dx.doi.org/10.1002/glia.21113
[55] Weyerbrock, A., Osterberg, N., Psarras, N., Baumer, B., Kogias, E., Werres, A., Bette, S., Saavedra, J.E., Keefer, L.K., and Papazoglou, A. (2012) JS-K, a Glutathione S-Transferase-Activated Nitric Oxide Donor with Antineoplastic Activity in Malignant Gliomas. Neurosurgery, 70, 497-510.
http://dx.doi.org/10.1227/NEU.0b013e31823209cf
[56] Sontheimer, H. and Bridges, R.J. (2012) Sulfasalazine for Brain Cancer Fits. Expert Opinion on Investigational Drugs, 21, 575-578. http://dx.doi.org/10.1517/13543784.2012.670634
[57] Lyons, S.A., Chung, W.J., Weaver, A.K., Ogunrinu, T. and Sontheimer, H. (2007) Autocrine Glutamate Signaling Promotes Glioma Cell Invasion. Cancer Research, 67, 9463-9471.
http://dx.doi.org/10.1158/0008-5472.CAN-07-2034
[58] Doxsee, D.W., Gout, P.W., Kurita, T., Lo, M., Buckley, A.R., Wang, Y., Xue, H., Karp, C.M., Cutz, J.C., Cunha, G.R., and Wang, Y.Z. (2007) Sulfasalazine-Induced Cystine Starvation: Potential Use for Prostate Cancer Therapy. The Prostate, 67, 162-171. http://dx.doi.org/10.1002/pros.20508
[59] Lang, W., Caldwell, G.W., Li, J., Leo, G.C., Jones, J.J. and Masucci, J.A. (2007) Biotransformation of Geldanamycin and 17-Allylamino-17-Demthoxygeldanamycin by Human Liver Microsomes: Reduction versus Oxidative Metabolism and Implications. Drug Metabolism and Disposition, 35, 21-29. http://dx.doi.org/10.1124/dmd.106.009639
[60] Turner, C.E. (2000) Paxillin Interactions. Journal of Cell Science, 113, 4139-4140.
[61] Gao, C.F., Xie, Q., Su, Y.L., Koeman, J., Khoo, S.K., Gustafson, M., Knudsen, B.S., Hay, R., Shinomiya, N. and Woude, G.F.V. (2005) Proliferation and Invasion: Plasticity in Tumor Cells. Proceedings of the National Academy of Sciences of the United States of America, 102, 10528-10533.
http://dx.doi.org/10.1073/pnas.0504367102
[62] Kardosh, A., Golden, E.B., Pyrko, P., Uddin, J., Hofman, F.M., Chen, T.C., Louie, S.G., Petasis, N.A. and Sch?nthal, A.H. (2008) Aggravated Endoplasmic Reticulum Stress as a Basis for Enhanced Glioblastoma Cell Killing by Bortezomib in Combination with Celecoxib or Its Non-Coxib Analogue, 2,5-Dimethyl-celecoxib. Cancer Research, 68, 843-851. http://dx.doi.org/10.1158/0008-5472.CAN-07-5555
[63] Teefy, A.M., Martin, J.E. and Kovacs, M.J. (2000) Warfarin Resistance Due to Sulfasalazine. Annals of Pharmacotherapy, 34, 1265-1268. http://dx.doi.org/10.1345/aph.10076
[64] Hall, S. and Ridone, J.P. (2001) A Case of Sulphasalazine Potentiating the Hypoprothombinemic Effect of Warfarin Resulting in Bleeding. Journal of Clinical Pharmacy and Therapeutics, 36, 246-248. http://dx.doi.org/10.1111/j.1365-2710.2010.01173.x

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.