Dietary Ascorbic Acid-Mediated Augmentation of Antitumor Activity and Protection Against Toxicities Induced by Cis-Diamminedichloroplatinum-(II) in Daltons Lymphoma-Bearing Mice -
DOI:
https://doi.org/10.6000/1929-2279.2013.02.02.6Keywords:
Ascorbic acid, Apoptosis, cis-Diamminedichloroplatinum-(II), Dalton’s lymphoma, Reduced glutathione, Hematotoxicity.Abstract
Cis-Diamminedichloroplatinum-(II) (CDDP) commonly known as cisplatin is considered as a major anticancer drug against a broad spectrum of malignancies. This study evaluates the modulatory effect of dietary ascorbic acid (AA) on the therapeutic efficacy of CDDP against murine ascites Daltons lymphoma (DL) and some tissue toxicities in tumor-bearing mice.
As compared to CDDP alone, the combination treatment with ascorbic acid (AA) plus CDDP showed better therapeutic efficacy against murine ascites Daltons lymphoma. DL cells treated with CDDP showed the appearance of apoptotic features involving fragmentation of nucleus into discrete masses and plasma membrane blebbing. As compared to CDDP alone, combination treatment caused an increase in the number of apoptotic DL cells. Reduced glutathione (GSH) level was noted to decrease in DL cells while it increased in kidney after combination treatment. Blood haemoglobin (Hb), red blood cells (RBCs) and white blood cells (eosinophils, basophils and lymphocytes) were also decreased after CDDP treatment while overall betterment in hematological parameters was noted after combination treatment. The analysis of renal function tests (RFT) and liver function tests (LFT) suggest an improvement against CDDP-induced liver and kidney toxicities after combination treatment.
The decrease in GSH levels particularly in DL cells and an increase in kidney and liver after combination treatment may have a role in the antitumor activity and decrease in CDDP-induced toxicity in the tumor-bearing host. Improvement in the LFT, RFT and hematological toxicities after combination treatment may have a beneficial effect in the improved survival of tumor-bearing mice.
References
Stewart BW, Kleihues P. Eds. World Cancer Report, IARC Press, Lyon, 2003; pp. 1-342. http://www.iarc.fr/en/ publications/pdfs-online/wcr/2008/wcr_2008
Rosenberg B. Fundamental studies with cisplatin. Cancer 1985; 55: 2303-16. http://dx.doi.org/10.1002/1097-0142(19850515)55:10<2303::AID-CNCR2820551002>3.0.CO;2-L
Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy an historical perspective and an update. Eur J Cancer 1998; 34: 1522-34. http://dx.doi.org/10.1016/S0959-8049(98)00224-X
Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 2011; 3: 1351-71. http://www.mdpi. com/2072-6694/3/1/1351
Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Perez JM. Biochemical mechanisms of cisplatin cytotoxicity. Anti-Cancer Agents Med Chem 2007; 7: 3-18. http://www. benthamscience.com/cmcaca/sample/cmcaca%207-1/0002W http://dx.doi.org/10.2174/187152007779314044
Prasad SB, Giri A, Khynriam D, Kharbangar A, Nicol BM, Lotha C. Cisplatin-mediated enzymatic changes in mice bearing ascites Dalton’s lymphoma. Medical Sci Res 1999; 27: 723-30. http://www.researchgate.net/journal/0269-8951_Medical_science_research
Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol 2008; 6: 1-18. http://www.ncbi.nlm.nih.gov/pubmed/ 19178659 http://dx.doi.org/10.1111/j.1476-5829.2007.00142.x
Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22: 7265-79. http://www.ncbi.nlm.nih.gov/pubmed/14576837 http://dx.doi.org/10.1038/sj.onc.1206933
Treskes M, Vander-Vijgh WJF. WR2721 as a modulator of cisplatin and carboplatin-induced side effects in comparison with other chemopreventive agent: a molecular approach. Cancer Chemother Pharmacol 1993; 33: 93-106. http://www.ncbi.nlm.nih.gov/pubmed/8261581 http://dx.doi.org/10.1007/BF00685326
Sanchez-Gonzalez PD, Lopez-Hernandez FJ, Perez-Barriocanal F, Morales AI, Lopez-Novoa JM. Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity. Nephrol Dial Transplant 2011; 26: 3484-95. http://www.ncbi.nlm.nih.gov/pubmed/21602180 http://dx.doi.org/10.1093/ndt/gfr195
Nicol BM, Prasad SB. The effects of cyclophosphamide alone and in combination with ascorbic acid against murine ascites Dalton’s lymphoma. Indian J Pharmacol 2006; 38: 260-65. http://www.bioline.org.br/pdf?ph06069 http://dx.doi.org/10.4103/0253-7613.27022
Park JH, Davis KR, Lee G, Jung M, Jung Y, Park J, et al. Ascorbic acid alleviates toxicity of paclitaxel without interfering with the anticancer efficacy in mice. Nutr Res 2012; 32: 873-83. http://www.ncbi.nlm.nih.gov/pubmed/ 23176798 http://dx.doi.org/10.1016/j.nutres.2012.09.011
Yedjou C, Thuisseu L, Tchounwou C, Gomes M, Howard C, Tchounwou P. Ascorbic acid potentiation of arsenic trioxide anticancer activity against acute promyelocytic leukemia. Arch Drug Info 2009; 2: 59-65. http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2805867/
Henson DE, Block G, Levine M. Ascorbic acid: Biological functions and relation to cancer. J Natl Cancer Inst 1991; 83: 547-50. http://dx.doi.org/10.1093/jnci/83.8.547
Verrax J, Buc-Calderon P. The controversial place of vitamin C in cancer treatment. Biochem Pharmacol 2008; 76: 1644-52. http://www.farm.ucl.ac.be/Full-texts-FARM/Verrax-2008-2 http://dx.doi.org/10.1016/j.bcp.2008.09.024
Kathleen A. Ascorbic acid in the prevention and treatment of cancer. Altern Med Rev 1998; 3: 174-86. http://summer-shouse.com/files/VCPreventandTx
Ohno S, Ohno Y, Suzuki N, Soma G, Inoue M. High-dose vitamin C [Ascorbic Acid] therapy in the treatment of patients with advanced cancer. Anticancer Res 2009; 29: 809-15. http://www.ncbi.nlm.nih.gov/pubmed/19414313
Leibovitz B, Schlesser J. Effect of L-ascorbic acid on leukemia development and breast cancer in various inbred strains of mice. In: Meyskens, F.L. and Prasad, K.N. (eds), Modulation and mediation of cancer by vitamins, Karger, Basel 1983; pp. 140-143. http://www.worldcat.org/title/ modulation-and-mediation-of-cancer-by-vitamins/oclc/ 9830026
Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, Rubin J, Frytak S. Failure of high-dose vitamin C [ascorbic acid] therapy to benefit patients with advanced cancer. A controlled trial. New Engl J Med 1979; 301: 687-90. http://europepmc.org/abstract/MED/384241 http://dx.doi.org/10.1056/NEJM197909273011303
Dunham WB, Zuckerkandl E, Reynolds R, Willoughby R, Marcuson R, Barth R, Pauling L. Effects of intake of L-ascorbic acid on the incidence of dermal neoplasms induced in mice by ultraviolet light. Proc Natl Acad Sci USA 1982; 79: 7532-36. http://dx.doi.org/10.1073/pnas.79.23.7532
Lee KW, Lee HJ, Kang KS, Lee CY. Preventive effects of vitamin C on carcinogenesis. Lancet 2002; 359: 172. http://www.ncbi.nlm.nih.gov/pubmed/11809299 http://dx.doi.org/10.1016/S0140-6736(02)07358-0
Surjyo B, Anisur Rahman KB. Protective action of an anti-oxidant [L-Ascorbic acid] against genotoxicity and cytotoxicity in mice during p-DAB-induced hepatocarcinogenesis. Indian J Cancer 2004; 41: 72-80. http://www.ncbi.nlm.nih.gov/ pubmed/15318012
Banič S. Vitamin C acts as a co-carcinogen to methylcholanthrene in guinea-pigs. Cancer Lett 1981; 11: 239-42. http://www.sciencedirect.com/science/journal/ 03043835/11/3 http://dx.doi.org/10.1016/0304-3835(81)90114-2
Fukushima S, Imaida K, Sakata T, Okamura T, Shibata M, Ito N. Promoting effects of sodium L-ascorbate on two stage urinary bladder carcinogenesis in rats. Cancer Res 1983; 43: 4454-57. http://cancerres.aacrjournals.org/content/43/9/4454. short
Shamberger RJ. Genetic toxicology of ascorbic acid. Mutat Res 1984; 133: 135-59. http://www.sciencedirect.com/ science/journal/01651110/133/2 http://dx.doi.org/10.1016/0165-1110(84)90005-8
Nefic H. The genotoxicity of vitamin C in vitro. Bosnian J Basic Med Sci 2008; 8: 141-46. http://bjbms.org/archives/ 2008-2/141-146
Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HW. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett 1996; 103: 183-89. http://www.ncbi.nlm.nih.gov/pubmed/8635156 http://dx.doi.org/10.1016/0304-3835(96)04212-7
Barbosa ALR, Pinheiro CA, Oliveira GJ, Moraes MO, Ribeiro RA, Vale ML, et al. Tumor bearing decreases systemic acute inflammation in rats- role of mast cell degranulation. Inflamm Res 2009; 58: 235-40. http://dx.doi.org/10.1007/s00011-008-8226-z
Goldie H, Felix MD. Growth characteristics of free tumor cells transformed serially in the peritoneal fluid of mouse. Cancer Res 1951; 11: 73-80. http://hwmaint.cancerres.aacrjournals. org/cgi/content/abstract/11/2/73
Sodhi A, Prasad SB. Ultrastructural and fluorescence microscopical observations on the effect of cis-dichlorodiammineplatinum [II] on the surface of tumor and normal cells. Indian J Exp Biol 1981; 19: 328-32. http://www.ncbi.nlm.nih.gov/pubmed/7196883
Prasad SB, Nicol BM, Rosangkima G, Amenla. Modulatory effect of ascorbic acid [vitamin c] on cyclophosphamide-mediated antitumor activity and mutagenicity in mice bearing ascites Dalton’s lymphoma. Int J Pharma Bio Sci 2010; 1: 1-20. http://www.ijpbs.net/issue-2/96
Baskic D, Popovic S, Ristic P, Arsenijevic NN. Analysis of cycloheximide-induced apoptosis in human leukocytes: Fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol Int 2006; 30: 924-32. http://www-13.all-portland.net/cbi/030/0924/ 0300924 http://dx.doi.org/10.1016/j.cellbi.2006.06.016
Verma AK, Prasad SB. Bioactive component, cantharidin from Mylabris cichorii and its antitumor activity against Ehrlich ascites carcinoma. Cell Biol Toxicol 2012; 28: 133-47. http://dx.doi.org/10.1007/s10565-011-9206-6
Sedlak J, Lindsay HR. Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissues with Ellman's reagent. Anal Biochem 1968; 25: 192-205. http://www.ncbi. nlm.nih.gov/pubmed/4973948 http://dx.doi.org/10.1016/0003-2697(68)90092-4
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-75. http://www.jbc.org/content/193/1/265. citation
Dacie JV, Lewis SM. Practical haematology, 5th ed. Churchill Livingstone: Edinburgh, New York 1975; pp. 21-67. http://trove.nla.gov.au/work/5980082?q&versionId=25659937
Li CJ, Chu CY, Huang LH, Wang MH, Sheu LF, Yeh JI, Hsu HY. Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo. Cancer Lett 2012; 319: 203-13. http://www.ncbi.nlm. nih.gov/pubmed/22306340 http://dx.doi.org/10.1016/j.canlet.2012.01.006
Taper HS, de Gerlache J, Lans M, Roberfroid M. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987; 40: 575-79. http://www.ncbi.nlm.nih.gov/pubmed/3666992 http://dx.doi.org/10.1002/ijc.2910400424
Nagy B, Mucsi I, Molnar J, Varga A, Thurzo L. Chemosensitizing effect of vitamin C in combination with 5-fluorouracil in vitro. In Vivo 2003; 17: 289-92. http://www. ncbi.nlm.nih.gov/pubmed/12929582
Chiang CD, Song EJ, Yang VC, Chao CC. Ascorbic acid increases drug accumulation and reverses vincristine resistance of human non-small-cell lung-cancer cells. Biochem J 1994; 301: 759-64. http://www.ncbi.nlm.nih.gov/ pubmed/7914401
Sarna S, Bhola RK. Chemo-immunotherapeutical studies on Dalton's lymphoma in mice using cisplatin and ascorbic acid: synergistic antitumor effect in vivo and in vitro. Arch Immunol Ther Exp 1993; 41: 327-33. http://www.ncbi.nlm.nih.gov/ pubmed/8010874
Heaney ML, Gardner JR, Karasavvas N, Golde DW, Scheinberg DA, Smith EA, O’Connor OA. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res 2008; 68: 8031-38. http://www.ncbi.nlm.nih.gov/ pubmed/18829561 http://dx.doi.org/10.1158/0008-5472.CAN-08-1490
Zou W, Yue P, Lin N, He M, Zhou Z, Lonial S, et al. Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells. Clin Cancer Res 2006; 12: 273-80. http://www.ncbi.nlm.nih.gov/pubmed/16397052 http://dx.doi.org/10.1158/1078-0432.CCR-05-0503
Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol 2007; 35: 495-16. http://www.ncbi.nlm.nih.gov/ pubmed/17562483 http://dx.doi.org/10.1080/01926230701320337
Gonzalez VM, Fuertes MA, Alonso C, Perez JM. Is cisplatin-induced cell death always produced by apoptosis? Mol Pharmacol 2001; 59: 657-63. http://www.ncbi.nlm.nih.gov/ pubmed/11259608
Gokhalé P, Patel T, Morrison MJ, Vissers MC. The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents. Apoptosis 2006; 11, 1737-46. http://www.ncbi.nlm.nih.gov/pubmed/16951922 http://dx.doi.org/10.1007/s10495-006-9787-3
An SH, Kang JH, Kim DH, Lee MS. Vitamin C increases the apoptosis via up-regulation p53 during cisplatin treatment in human colon cancer cells. BMB Reports 2011; 44: 211-16. http://www.ncbi.nlm.nih.gov/pubmed/21429301
Catani MV, Costanzo A, Savini I, Levrero M, De laurenzi V, Wang JYJ, et al. Ascorbate up-regulates MLH1 [Mut L homologue-1] and p73: implications for the cellular response to DNA damage. Biochem J 2002; 364: 441-47. http://www. ncbi.nlm.nih.gov/pubmed/12023887 http://dx.doi.org/10.1042/BJ20011713
Kang JS, Cho D, Kim YI, Hahm E, Yang Y, Kim D, et al. L-ascorbic acid [vitamin C] induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway. Cancer Immunol Immunother 2003; 52: 693-98. http://www.ncbi.nlm.nih.gov/pubmed/12827307 http://dx.doi.org/10.1007/s00262-003-0407-6
Wang W, Ballatori N. Endogenous glutathione conjugates: occurrence and biological functions. Pharmacol Rev 1998; 50: 335-56. http://www.ncbi.nlm.nih.gov/pubmed/9755286
Estrela JM, Hernandez R, Terradez P, Asensi M, Puertes IR, Vina J. Regulation of glutathione metabolism in Ehrlich ascites tumour cells. Biochem J 1992; 286: 257-62. http://www.biochemj.org/bj/286/0257/2860257
Shaw JP, Chou IN. Elevation of intracellular glutathione content associated with mitogenic stimulation of quiescent fibroblasts. J Cell Physiol 1986; 129: 193-98. http://www.ncbi. nlm.nih.gov/pubmed/3771652 http://dx.doi.org/10.1002/jcp.1041290210
Zunino F, Pratesi G, Micheloni A, Cavaletti E, Sala F, Tofanetti O. Protective effect of reduced glutathione against cisplatin-induced renal and systemic toxicity and its influence on the therapeutic activity of the antitumor drug. Chem Biol Interact 1989; 70: 89-101. http://www.ncbi.nlm.nih.gov/ pubmed/2736678 http://dx.doi.org/10.1016/0009-2797(89)90065-3
Harder HC, Rosenberg B. Inhibitory effects of antitumor platinum compounds on DNA, RNA and protein synthesis in mammalian cells in vitro. Int J Cancer 1970; 6: 207-16. http://dx.doi.org/10.1002/ijc.2910060207
Heminger KA, Hartson SD, Rogers J, Matts RL. Cisplatin inhibits protein synthesis in rabbit reticulocyte lysate by causing an arrest in elongation. Arch Biochem Biophys 1997; 344: 200-207. http://www.ncbi.nlm.nih.gov/pubmed/9244398 http://dx.doi.org/10.1006/abbi.1997.0198
Wood PA, Hrushesky WJ. Cisplatin-associated anemia: an erythropoietin deficiency syndrome. J Clin Invest 1995; 95: 1650-59. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC295669/ http://dx.doi.org/10.1172/JCI117840
Unami A, Nishina N, Terai T, Sato S, Tamura T, Noda K, Mine Y. Effects of cisplatin on erythropoietin production in rats. J Toxicol Sci 1996; 21: 157-65. http://www.ncbi.nlm.nih. gov/pubmed/8887884 http://dx.doi.org/10.2131/jts.21.3_157
Ruka W, Rutkowski P, Kaminska J, Rysinska A, Steffen J. Alterations of routine blood tests in adult patients with soft tissue sarcomas: Relationships to cytokine serum levels and prognostic significance. Ann Oncol 2001; 12: 1423-32. http://www.ncbi.nlm.nih.gov/pubmed/11762815 http://dx.doi.org/10.1023/A:1012527006566
El-Sayed el-SM, Abd-Ellah MF, Attia SM. Protective effect of captopril against cisplatin-induced nephrotoxicity in rats. Pak J Pharm Sci 2008; 21: 255-61. http://www.pjps.pk/cd-pjps-21-3-08/paper-9
Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Internat 2008; 73: 994-1007. http://ic.ucsc.edu/~drsmith/metx270/html/Pabla%20 and%20Dong%202008 http://dx.doi.org/10.1038/sj.ki.5002786
De Martinis BS, Bianchi MD. Effect of vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats. Pharmacol Res 2001; 44: 317-20. http://www.ncbi.nlm.nih.gov/pubmed/11592867 http://dx.doi.org/10.1006/phrs.2001.0860
Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediat 2007; 74: 663-71. http://www. ncbi.nlm.nih.gov/pubmed/17699976 http://dx.doi.org/10.1007/s12098-007-0118-7
Downloads
Published
How to Cite
Issue
Section
