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Differential Behaviour of Selenium Analogs against Anticancer Drug Induced Apoptosis of Lymphocytes in Human Peripheral Blood

  • Elango, Sonaa (Department of Life Science, School of Natural Sciences, University of Suwon) ;
  • Subbiah, Usha (Human Genetics Laboratory, Central Research Facility, Sree Balaji Medical and Dental College and Hospital, Bharath University) ;
  • Jain, Jeong (Department of Bio-Medical Sciences, Catholic University of Daegu)
  • Published : 2016.05.01

Abstract

Sensitising cancer cells and at the same time desensitizing normal cells is a double task in cancer management. Agents which can combat the debilitating side effects of cancer therapeutics and simultaneously synergize with anticancer agents in specifically targeting cancer cells are needed. Selenium, a proven anticarcinogen, gains due importance in terms of its efficacy to combat the side effects of cancer therapy. This study is a comparative analysis of the chemoprotective effects of selenium compounds, methyl selenol (generated from organic selenomethionine (5mmol/L ; METase 40U/L)) and sodium selenite (inorganic form)($30{\mu}M$) in peripheral blood human lymphocytes exposed to cisplatin and mitomycin. Biochemical alterations occurring in many cells during apoptosis include loss of plasma membrane phospholipid asymmetry, DNA fragmentation, and activation of caspase-3. The present study demonstrated that the selenium metabolite and selenite are efficient in protecting lymphocytes undergoing DNA damage and exerted their activity by reducing caspase 3 expression. Interestingly organic methylselenol (MeSe) was found to offer more protective effects compared to inorganic selenite (SeL), by reducing the induction of apoptosis by the cytotoxic agents. This suggests that MeSe and to a lesser extent selenite might have potential for assessment in clinical trials and could be considered as strong candidates in pharmacogenomics or in the nutriprotective arena.

Keywords

Acknowledgement

Supported by : Catholic University of Daegu, University of Suwon

References

  1. Auer G, Eriksson E, Azaved E et al (1984). Prognostic significance of nuclear DNA content in Mammary adenocarcinomas in humans. Cancer Res, 44, 394-6.
  2. Alpsoy L, Agar G, Ikbal M (2009). Protective role of vitamins A, C, and E against the genotoxic damage induced by aflatoxin B1 in cultured human lymphocytes. Toxicol Health, 25, 183-8. https://doi.org/10.1177/0748233709106068
  3. Andea L, Isgro G, Pleguezueli M et al (2009). Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis. World J Hepatol, 1, 48-61. https://doi.org/10.4254/wjh.v1.i1.48
  4. Alcindor T, Beauger N (2011). Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol, 18, 18-25.
  5. Abbas T, Olivier M, Lopez J, Houser S, Xiao G, Suresh kumar G, et al (2002). Differential activation of p53 by the various adducts of mitomycin C. J BiolChem, 277, 40513-9.
  6. Bedner E, Li X, Gorczyca W, Melamed MR, Darzynkiewicz Z (1999). Analysis of apoptosis by laser scanning cytometry. Cytometry, 35, 181-95. https://doi.org/10.1002/(SICI)1097-0320(19990301)35:3<181::AID-CYTO1>3.0.CO;2-5
  7. Battin EE, Brumaghim JL (2009). Antioxidant activity of sulfur and selenium: a review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms. Cell Biochem, 55, 1-23.
  8. Bargonetti J, Champeil E, Tomasz M (2010), Differential Toxicity of DNA Adducts of Mitomycin C. J Nucleic Acids, 4, 1-6.
  9. Brozmanova J, Manikova D, Vlckova V, Chovanec M (2010). Selenium: a double-edged sword for defense and offence in cancer. Arch Toxicol, 84, 919-38. https://doi.org/10.1007/s00204-010-0595-8
  10. Brozmanova J (2011). Selenium and cancer: from prevention to treatment. Klin Onko, 24,171-9.
  11. Castaldo SA, Freitas JR, Conchinha NV, Madureira PA (2016). The Tumorigenic Roles of the Cellular REDOX Regulatory Systems. Oxidative Med Cell Long, 17.
  12. Drake EN (2006). Cancer chemoprevention: selenium as a prooxidant, not an antioxidant. Med Hypotheses, 67, 318-22. https://doi.org/10.1016/j.mehy.2006.01.058
  13. Dasari S, Tchounwou PB (2014). Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol, 0, 364-78.
  14. Ellman GL (1959). Tissue sulfhydryl groups. Arch Biochem Biophys, 82, 70-7. https://doi.org/10.1016/0003-9861(59)90090-6
  15. Elango N, Samuel S, Cinnakannu P (2006). Enzymatic and Non enzymatic antioxidant status in stage (III) human oral squamous cell carcinoma and treated with radical radiotherapy: Influence of selenium supplementation. Clinica Chimica Acta, 373, 92-8. https://doi.org/10.1016/j.cca.2006.05.021
  16. El-Mazary AM, Aziz RA, Mahmoud RA, El-Said MA, Mohammed NR (2015). Correlations between maternal and neonatal serum selenium levels in full term neonates with hypoxic ischemic encephalopathy. Ital J Pediatr, 41, 83. https://doi.org/10.1186/s13052-015-0185-8
  17. Ganther HE (1999). Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxinreductase. Carcinogenesis, 20, 1657-66. https://doi.org/10.1093/carcin/20.9.1657
  18. Guo CH, Hsia S, Shih M, Hsieh FC, Chen PC (2015). Effects of Selenium Yeast on Oxidative Stress, Growth Inhibition and Apoptosis in Human Breast Cancer Cells. Int J Med Sci, 12, 748-58. https://doi.org/10.7150/ijms.12177
  19. Ghosh P, Roy SS, Basu A, Bhattacharjee A, Bhattacharya S (2015). Sensitization of cisplatin therapy by a naphthalimide based organoselenium compound through modulation of antioxidant enzymes and p53 mediated apoptosis. Free Radic Res, 49, 453-71. https://doi.org/10.3109/10715762.2015.1012079
  20. Jayaprakash R, Ramesh V, Sridhar MP, Sasikala C (2015). Antioxidant activity of ethanolic extract of Tinospora cordifolia on N-nitrosodiethylamine (diethylnitrosamine) induced liver cancer in male Wister albino rats. J Pharm Bioallied Sci, 7, S40-5. https://doi.org/10.4103/0975-7406.155791
  21. Kiernan JA (1981). Methods for nucleic acid. In histological and histochemical methods theory and practical. 2nd ed. Pergaman Press Oxford 104-7.
  22. Menter DG, Sabichi AL, Lippman SM (2000). Selenium effects on prostate cell growth. Cancer Epidemiol Biomarkers Prev, 9, 171-1182.
  23. Mueke R, Schomburg L, Buentzel J, et al (2010). Selenium or no selenium- that is the question in tumor patients: a new controversy. Integr Cancer Ther, 9, 136-41. https://doi.org/10.1177/1534735410367648
  24. Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-8. https://doi.org/10.1016/0003-2697(79)90738-3
  25. Rotruck JT, Pope AL, Ganther HE, et al (1973). Selenium: Biochemical role as a component of glutathione peroxidase. Science, 179, 558 - 90. https://doi.org/10.1126/science.179.4073.558
  26. Stadtman TC (1991). Biosynthesis and function of selenocysteine-containing enzymes. J Biol Chem, 266, 16257-60.
  27. Singh NP, Graham MM, Singh V, Khan A (1995). Induction of DNA single-strand breaks in human lymphocytes by low doses of Y-rays. Int J Radiat Biol, 68, 563-9. https://doi.org/10.1080/09553009514551551
  28. Spallholz JE (1997). Free radical generation by selenium compounds and their prooxidant toxicity. Biomed Environ Sci, 10, 260-70.
  29. Santos RA, Takahashi CS (2008). Anticlastogenic and antigenotoxic effects of selenomethionine on doxorubicininduced damage in vitro in human lymphocytes. Food ChemToxicol, 46, 671-7. https://doi.org/10.1016/j.fct.2007.09.090
  30. Terazawa R, Garud DR, Hamada N, et al (2010). Identification of organoselenium compounds that possess chemopreventive properties in human prostate cancer LNCaP cells. Bioorg Med Chem, 24, 7001-8.
  31. Tatsukawa H, Sano T, Fukaya Y et al (2011). Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells. Molecular Cancer, 10, 1-11. https://doi.org/10.1186/1476-4598-10-1
  32. Tynga IM, Abrahamse H (2015). Cell death pathways and phthalocyanine as an efficient agent for photodynamic cancer therapy. Int J Mol Sci, 16, 10228-41. https://doi.org/10.3390/ijms160510228
  33. Weber SU, Lehmann LE, Schewe JC, et al (2008). Low serum ${\alpha}$-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis. Bio Factor, 33, 107-19.
  34. Yeo JE, Kang SK (2007). Selenium effectively inhibits ROS-mediated apoptotic neural precursor cell death in vitro and in vivo in traumatic brain injury. Biochim Biophys Acta, 1772, 1199-210. https://doi.org/10.1016/j.bbadis.2007.09.004
  35. Zhou N, Xiao H, Li TK, et al (2003).DNA damage-mediated apoptosis induced by selenium compounds. J Biol Chem, 278, 29532-37. https://doi.org/10.1074/jbc.M301877200
  36. Zeng H, Wu M, Botnen JH (2009). Methylselenol, a Selenium Metabolite, Induces Cell Cycle Arrest in G1 Phase and Apoptosis via the Extracellular-Regulated Kinase 1/2 Pathway and Other Cancer Signaling Genes1-3. J Nutr, 139, 1613-1618. https://doi.org/10.3945/jn.109.110320