SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Grad, J. M. Articles by Boise, L. H. Search for Related Content PubMed PubMed Citation Articles by Grad, J. M. Articles by Boise, L. H. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2001, Vol. 98, No. 3, pp. 805-813 NEOPLASIA Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells Jennifer M. Grad, Nizar J. Bahlis, Isildinha Reis, Marc M. Oshiro, William S. Dalton, and Lawrence H. Boise From the Department of Microbiology and Immunology, Division of Hematology and Oncology, Sylvester Cancer Center, University of Miami School of Medicine, Florida; and the H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL. Multiple myeloma (MM) is a clonal B-cell malignancy characterized by slow-growing plasma cells in the bone marrow (BM). Patients with MM typically respond to initial chemotherapies; however, essentially all progress to a chemoresistant state. Factors that contribute to the chemorefractory phenotype include modulation of free radical scavenging, increased expression of drug efflux pumps, and changes in gene expression that allow escape from apoptotic signaling. Recent data indicate that arsenic trioxide (As2O3) induces remission of refractory acute promyelocytic leukemia and apoptosis of cell lines overexpressing Bcl-2 family members; therefore, it was hypothesized that chemorefractory MM cells would be sensitive to As2O3. As2O3 induced apoptosis in 4 human MM cell lines: 8226/S, 8226/Dox40, U266, and U266/Bcl-xL. The addition of interleukin-6 had no effect on cell death. Glutathione (GSH) has been implicated as an inhibitor of As2O3-induced cell death either through conjugating As2O3 or by sequestering reactive oxygen induced by As2O3. Consistent with this possibility, increasing GSH levels with N-acetylcysteine attenuated As2O3 cytotoxicity. Decreases in GSH have been associated with ascorbic acid (AA) metabolism. Clinically relevant doses of AA decreased GSH levels and potentiated As2O3-mediated cell death of all 4 MM cell lines. Similar results were obtained in freshly isolated human MM cells. In contrast, normal BM cells displayed little sensitivity to As2O3 alone or in combination with AA. Together, these data suggest that As2O3 and AA may be effective antineoplastic agents in refractory MM and that AA might be a useful adjuvant in GSH-sensitive therapies. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. C. Platanias Biological Responses to Arsenic Compounds J. Biol. Chem., July 10, 2009; 284(28): 18583 - 18587. [Abstract] [Full Text] [PDF] A. A. Morales, D. Gutman, P. J. Cejas, K. P. Lee, and L. H. Boise Reactive Oxygen Species Are Not Required for an Arsenic Trioxide-induced Antioxidant Response or Apoptosis J. Biol. Chem., May 8, 2009; 284(19): 12886 - 12895. [Abstract] [Full Text] [PDF] S. M. Matulis, A. A. Morales, L. Yehiayan, C. Croutch, D. Gutman, Y. Cai, K. P. Lee, and L. H. Boise Darinaparsin induces a unique cellular response and is active in an arsenic trioxide-resistant myeloma cell line Mol. Cancer Ther., May 1, 2009; 8(5): 1197 - 1206. [Abstract] [Full Text] [PDF] L. J. Hoffer, M. Levine, S. Assouline, D. Melnychuk, S. J. Padayatty, K. Rosadiuk, C. Rousseau, L. Robitaille, and W. H. Miller Jr Phase I clinical trial of i.v. ascorbic acid in advanced malignancy Ann. Onc., November 1, 2008; 19(11): 1969 - 1974. [Abstract] [Full Text] [PDF] P. Lunghi, N. Giuliani, L. Mazzera, G. Lombardi, M. Ricca, A. Corradi, A. M. Cantoni, L. Salvatore, R. Riccioni, A. Costanzo, et al. Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways Blood, September 15, 2008; 112(6): 2450 - 2462. [Abstract] [Full Text] [PDF] A. A. Morales, D. Gutman, K. P. Lee, and L. H. Boise BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma Blood, May 15, 2008; 111(10): 5152 - 5162. [Abstract] [Full Text] [PDF] B. Dolniak, E. Katsoulidis, N. Carayol, J. K. Altman, A. J. Redig, M. S. Tallman, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, and L. C. Platanias Regulation of Arsenic Trioxide-induced Cellular Responses by Mnk1 and Mnk2 J. Biol. Chem., May 2, 2008; 283(18): 12034 - 12042. [Abstract] [Full Text] [PDF] J. K. Altman, P. Yoon, E. Katsoulidis, B. Kroczynska, A. Sassano, A. J. Redig, H. Glaser, A. Jordan, M. S. Tallman, N. Hay, et al. Regulatory Effects of Mammalian Target of Rapamycin-mediated Signals in the Generation of Arsenic Trioxide Responses J. Biol. Chem., January 25, 2008; 283(4): 1992 - 2001. [Abstract] [Full Text] [PDF] J. R. Berenson, J. Matous, R. A. Swift, R. Mapes, B. Morrison, and H. S. Yeh A Phase I/II Study of Arsenic Trioxide/Bortezomib/Ascorbic Acid Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma Clin. Cancer Res., March 15, 2007; 13(6): 1762 - 1768. [Abstract] [Full Text] [PDF] D. Chen, R. Chan, S. Waxman, and Y. Jing Buthionine Sulfoximine Enhancement of Arsenic Trioxide-Induced Apoptosis in Leukemia and Lymphoma Cells Is Mediated via Activation of c-Jun NH2-Terminal Kinase and Up-regulation of Death Receptors Cancer Res., December 1, 2006; 66(23): 11416 - 11423. [Abstract] [Full Text] [PDF] P. Kannan-Thulasiraman, E. Katsoulidis, M. S. Tallman, J. S. C. Arthur, and L. C. Platanias Activation of the Mitogen- and Stress-activated Kinase 1 by Arsenic Trioxide J. Biol. Chem., August 11, 2006; 281(32): 22446 - 22452. [Abstract] [Full Text] [PDF] N. Giafis, E. Katsoulidis, A. Sassano, M. S. Tallman, L. S. Higgins, A. R. Nebreda, R. J. Davis, and L. C. Platanias Role of the p38 Mitogen-Activated Protein Kinase Pathway in the Generation of Arsenic Trioxide-Dependent Cellular Responses. Cancer Res., July 1, 2006; 66(13): 6763 - 6771. [Abstract] [Full Text] [PDF] L. Catley and K. C. Anderson Velcade and Vitamin C: Too Much of a Good Thing? Clin. Cancer Res., January 1, 2006; 12(1): 3 - 4. [Full Text] [PDF] E. A. Obeng and L. H. Boise Caspase-12 and Caspase-4 Are Not Required for Caspase-dependent Endoplasmic Reticulum Stress-induced Apoptosis J. Biol. Chem., August 19, 2005; 280(33): 29578 - 29587. [Abstract] [Full Text] [PDF] T. Nakazato, K. Ito, Y. Ikeda, and M. Kizaki Green Tea Component, Catechin, Induces Apoptosis of Human Malignant B Cells via Production of Reactive Oxygen Species Clin. Cancer Res., August 15, 2005; 11(16): 6040 - 6049. [Abstract] [Full Text] [PDF] A. Chin, S. Liu, J. Ting-Chan, and M. A. Gill Extended stability of ascorbic acid in 5% dextrose injection and 0.9% sodium chloride injection Am. J. Health Syst. Pharm., May 15, 2005; 62(10): 1073 - 1074. [Full Text] [PDF] N. Karasavvas, J. M. Carcamo, G. Stratis, and D. W. Golde Vitamin C protects HL60 and U266 cells from arsenic toxicity Blood, May 15, 2005; 105(10): 4004 - 4012. [Abstract] [Full Text] [PDF] A. M. Ramos, C. Fernandez, D. Amran, P. Sancho, E. de Blas, and P. Aller Pharmacologic inhibitors of PI3K/Akt potentiate the apoptotic action of the antileukemic drug arsenic trioxide via glutathione depletion and increased peroxide accumulation in myeloid leukemia cells Blood, May 15, 2005; 105(10): 4013 - 4020. [Abstract] [Full Text] [PDF] D. Douer and M. S. Tallman Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies J. Clin. Oncol., April 1, 2005; 23(10): 2396 - 2410. [Abstract] [Full Text] [PDF] S. Trudel, Z. H. Li, E. Wei, M. Wiesmann, H. Chang, C. Chen, D. Reece, C. Heise, and A. K. Stewart CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma Blood, April 1, 2005; 105(7): 2941 - 2948. [Abstract] [Full Text] [PDF] M. J. Gonzalez, J. R. Miranda-Massari, E. M. Mora, A. Guzman, N. H. Riordan, H. D. Riordan, J. J. Casciari, J. A. Jackson, and A. Roman-Franco Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later Integr Cancer Ther, March 1, 2005; 4(1): 32 - 44. [Abstract] [PDF] L. Zhou, Y. Jing, M. Styblo, Z. Chen, and S. Waxman Glutathione-S-transferase {pi} inhibits As2O3-induced apoptosis in lymphoma cells: involvement of hydrogen peroxide catabolism Blood, February 1, 2005; 105(3): 1198 - 1203. [Abstract] [Full Text] [PDF] Z. Diaz, M. Colombo, K. K. Mann, H. Su, K. N. Smith, D. S. Bohle, H. M. Schipper, and W. H. Miller Jr Trolox selectively enhances arsenic-mediated oxidative stress and apoptosis in APL and other malignant cell lines Blood, February 1, 2005; 105(3): 1237 - 1245. [Abstract] [Full Text] [PDF] A. M. Evens, P. Lecane, D. Magda, S. Prachand, S. Singhal, J. Nelson, R. A. Miller, R. B. Gartenhaus, and L. I. Gordon Motexafin gadolinium generates reactive oxygen species and induces apoptosis in sensitive and highly resistant multiple myeloma cells Blood, February 1, 2005; 105(3): 1265 - 1273. [Abstract] [Full Text] [PDF] T. Sanchez Alcaraz, P. Kerkhofs, M. Reichert, R. Kettmann, and L. Willems Involvement of Glutathione as a Mechanism of Indirect Protection against Spontaneous Ex Vivo Apoptosis Associated with Bovine Leukemia Virus J. Virol., June 15, 2004; 78(12): 6180 - 6189. [Abstract] [Full Text] [PDF] X.-Y. Pei, Y. Dai, and S. Grant Synergistic Induction of Oxidative Injury and Apoptosis in Human Multiple Myeloma Cells by the Proteasome Inhibitor Bortezomib and Histone Deacetylase Inhibitors Clin. Cancer Res., June 1, 2004; 10(11): 3839 - 3852. [Abstract] [Full Text] [PDF] S. J. Padayatty, H. Sun, Y. Wang, H. D. Riordan, S. M. Hewitt, A. Katz, R. A. Wesley, and M. Levine Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use Ann Intern Med, April 6, 2004; 140(7): 533 - 537. [Abstract] [Full Text] [PDF] W.-C. Chou, C. Jie, A. A. Kenedy, R. J. Jones, M. A. Trush, and C. V. Dang Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells PNAS, March 30, 2004; 101(13): 4578 - 4583. [Abstract] [Full Text] [PDF] A. M. Evens, S. Prachand, B. Shi, M. Paniaqua, L. I. Gordon, and R. B. Gartenhaus Imexon-Induced Apoptosis in Multiple Myeloma Tumor Cells Is Caspase-8 Dependent Clin. Cancer Res., February 15, 2004; 10(4): 1481 - 1491. [Abstract] [Full Text] [PDF] D. M. Beaupre, E. Cepero, E. A. Obeng, L. H. Boise, and M. G. Lichtenheld R115777 induces Ras-independent apoptosis of myeloma cells via multiple intrinsic pathways Mol. Cancer Ther., February 1, 2004; 3(2): 179 - 186. [Abstract] [Full Text] [PDF] M. Porosnicu, A. Mian, and G. N. Barber The Oncolytic Effect of Recombinant Vesicular Stomatitis Virus Is Enhanced by Expression of the Fusion Cytosine Deaminase/Uracil Phosphoribosyltransferase Suicide Gene Cancer Res., December 1, 2003; 63(23): 8366 - 8376. [Abstract] [Full Text] [PDF] J. McCafferty-Grad, N. J. Bahlis, N. Krett, T. M. Aguilar, I. Reis, K. P. Lee, and L. H. Boise Arsenic trioxide uses caspase-dependent and caspase-independent death pathways in myeloma cells Mol. Cancer Ther., November 1, 2003; 2(11): 1155 - 1164. [Abstract] [Full Text] [PDF] A. Yacoub, C. Mitchell, J. Brannon, E. Rosenberg, L. Qiao, R. McKinstry, W. M. Linehan, Z.-s. Su, D. Sarkar, I. V. Lebedeva, et al. MDA-7 (Interleukin-24) Inhibits the Proliferation of Renal Carcinoma Cells and Interacts with Free Radicals to Promote Cell Death and Loss of Reproductive Capacity Mol. Cancer Ther., July 1, 2003; 2(7): 623 - 632. [Abstract] [Full Text] [PDF] S. Sturlan, M. Baumgartner, E. Roth, and T. Bachleitner-Hofmann Docosahexaenoic acid enhances arsenic trioxide-mediated apoptosis in arsenic trioxide-resistant HL-60 cells Blood, June 15, 2003; 101(12): 4990 - 4997. [Abstract] [Full Text] [PDF] W. S. Dalton Targeting the Mitochondria: An Exciting New Approach to Myeloma Therapy: Commentary re: N. J. Bahlis et al., Feasibility and Correlates of Arsenic Trioxide Combined with Ascorbic Acid-mediated Depletion of Intracellular Glutathione for the Treatment of Relapsed/Refractory Multiple Myeloma. Clin. Cancer Res., 8: 3658-3668, 2002. Clin. Cancer Res., December 1, 2002; 8(12): 3643 - 3645. [Full Text] [PDF] N. J. Bahlis, J. McCafferty-Grad, I. Jordan-McMurry, J. Neil, I. Reis, M. Kharfan-Dabaja, J. Eckman, M. Goodman, H. F. Fernandez, L. H. Boise, et al. Feasibility and Correlates of Arsenic Trioxide Combined with Ascorbic Acid-mediated Depletion of Intracellular Glutathione for the Treatment of Relapsed/Refractory Multiple Myeloma Clin. Cancer Res., December 1, 2002; 8(12): 3658 - 3668. [Abstract] [Full Text] [PDF] A. Verma, M. Mohindru, D. K. Deb, A. Sassano, S. Kambhampati, F. Ravandi, S. Minucci, D. V. Kalvakolanu, and L. C. Platanias Activation of Rac1 and the p38 Mitogen-activated Protein Kinase Pathway in Response to Arsenic Trioxide J. Biol. Chem., November 15, 2002; 277(47): 44988 - 44995. [Abstract] [Full Text] [PDF] Y. Dai, T. H. Landowski, S. T. Rosen, P. Dent, and S. Grant Combined treatment with the checkpoint abrogator UCN-01 and MEK1/2 inhibitors potently induces apoptosis in drug-sensitive and -resistant myeloma cells through an IL-6-independent mechanism Blood, October 16, 2002; 100(9): 3333 - 3343. [Abstract] [Full Text] [PDF] W. H. Miller Jr., H. M. Schipper, J. S. Lee, J. Singer, and S. Waxman Mechanisms of Action of Arsenic Trioxide Cancer Res., July 15, 2002; 62(14): 3893 - 3903. [Abstract] [Full Text] [PDF] W. H. Miller Jr. Molecular Targets of Arsenic Trioxide in Malignant Cells Oncologist, April 1, 2002; 7(90001): 14 - 19. [Abstract] [Full Text] [PDF] M. A. Hussein Nontraditional Cytotoxic Therapies for Relapsed/Refractory Multiple Myeloma Oncologist, April 1, 2002; 7(90001): 20 - 29. [Abstract] [Full Text] [PDF] R. B. Gartenhaus, S. N. Prachand, M. Paniaqua, Y. Li, and L. I. Gordon Arsenic Trioxide Cytotoxicity in Steroid and Chemotherapy-resistant Myeloma Cell Lines: Enhancement of Apoptosis by Manipulation of Cellular Redox State Clin. Cancer Res., February 1, 2002; 8(2): 566 - 572. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020