Document Type : Original Article
Authors
1 Associate Professor, Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
2 Pharmacist, Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
3 Veterinarian, Department of Veterinary, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
4 Assistant Professor, Department of Medicinal Chemistry, Faculty of Pharmacy & Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Abstract
Background: Although advances in cancer therapy continue to develop, the overall survival rate is poor for some cancer cases. The search for a new adjuvant strategy is the focus of cancer treatment. There is some evidence suggesting a change in the mechanism of cell function by a change in the content of deuterium in the medium. So, the aim of this study was to investigate the effect of deuterium depleted water (DDW) and deuterium enriched water (DEW) on the cell growth and cytotoxicity of two A549 and HepG2 cell lines.
Methods: TheA549 and HepG2 cell lines were cultured in media at different concentrations of deuterium and different exposure times. Cell proliferation was carried out by trypan blue dye exclusion technique. The cytotoxicity effects of DEW and DDW were determined by MTT assay on different exposure times (24, 48 and 72 h).
Results: In this study, DEW acted as a dose- response growth inhibitor at deuterium concentration of 50×103 ppm and greater, while no considerable effect was seen upon short and long term exposures to DDW (31 ppm and 127 ppm deuterium). Both DEW and DDW at used deuterium concentrations were found not to be toxic on the studied cell lines.
Conclusion: In conclusion, long term treatment with DEW could inhibit the proliferation of A549/HepG2 cell lines. Therefore, it can be considered as an adjuvant in cancer therapy.
Keywords
- Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin2014; 64(1):9-29.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009; 59(4):225-49.
- Rundel PW, Ehleringer JR, Nagy KA. Stable Isotopes in Ecological Research. New York: Springer; 1989.
- Somlyai G, Molnar M, Laskay G, Szabo M, Berkenyi T, Guller I, et al. Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion. Orv Hetil 2010; 151(36):1455-60. [In Hungarian].
- Somlyai G, Jancso G, Jakli G, Vass K, Barna B, Lakics V, et al. Naturally occurring deuterium is essential for the normal growth rate of cells. FEBS Lett 1993; 317(1-2):1-4.
- Uemura T, Moritake K, Akiyama Y, Kimura Y, Shingu T, Yamasaki T. Experimental validation of deuterium oxide-mediated antitumoral activity as it relates to apoptosis in murine malignant astrocytoma cells. J Neurosurg 2002; 96(5):900-8.
- Bahk JY, Lee JH, Chung HS, Lee HY, Chung BC, Park MS, et al. Anticancer effect of deuterium oxide on a bladder cancer cell related to Bcl-2 and Bax. J Ind Eng Chem 2007; 13(4):501-7.
- Bader Y, Hartmann J, Horvath Z, Saiko P, Grusch M, Madlener S, et al. Synergistic effects of deuterium oxide and gemcitabine in human pancreatic cancer cell lines. Cancer Lett 2008; 259(2):231-9.
- Cong FS, Zhang YR, Sheng HC, Ao ZH, Zhang SY, Wang JY. Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis. Exp Ther Med 2010; 1(2):277-83.
- Hartmann J, Bader Y, Horvath Z, Saiko P, Grusch M, Illmer C, et al. Effects of heavy water (D2O) on human pancreatic tumor cells. Anticancer Res 2005; 25(5):3407-11.
- Peterson J. Animal cell culture: a practical approach. Yale J Biol Med 1993; 66(4):336-7.
- Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell 2004; 5(3):215-9.
- Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology 2008; 48(6):2047-63.
- Hassanzade A, Mandegary A, Sharif E, Rasooli R, Mohammadnejad R, Masomi-Ardekani Y. Cyclooxygenase inhibitors combined with deuterium Enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways. Iran J Basic Med Sci 2018; 21(5):508-16.
- Somlyai G. Pharmaceutical products for curing tumorous diseases and process for preparing same. [cited October 30, 2019]. Available from: http://www.google.com/patents/US5855921.
- Kushner DJ, Baker A, Dunstall TG. Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol 1999; 77(2):79-88.
- Blagojevic N, Storr G, Allen BJ, Hatanaka H, Nakagawa H. Role of heavy water in boron neutron capture therapy. In: Zamenhof RG, Solares GR, Harling OK. Topics in Dosimetry and Treatment Planning for Neutron Capture Therapy. USA: Advanced Medical; 1994.
- Collins ML, Eng S, Hoh R, Hellerstein MK. Measurement of mitochondrial DNA synthesis in vivo using a stable isotope-mass spectrometric technique. J Appl Physiol (1985) 2003; 94(6):2203-11.
- Bogdahn U, Bauer A, Haase A. Deuterium-containing pharmaceutical compositions for destroying tumors. [cited October 30, 2019]. Available from: https://patents.google.com/patent/WO1996003996A1/en.
- Leonard PJ, Mullins JM. D2O induced alterations of mitosis in PtK1 cells. Exp Cell Res 1987; 172(1):204-211.
- Katz JJ, Crespi HL, Hasterlik RJ, Thomson JF, Finkel AJ. Some observations on biological effects of deuterium, with special reference to effects on neoplastic processes. J Natl Cancer Inst1957; 18(5):641-59.
- Biggs MW, Eiselein JE, Wilcox G. Observations on murine leukemia treated with deuterium and X-ray. Cancer Res 1963; 23:1059-62.
- Laeng RH, Mini RL, Laissue JA, Schindler R. Radioprotection of cultured cells by preincubation in medium containing deuterium oxide. International Journal of Radiation Biology 1991; 59(1):165-739.
- Gross PR, Spindel W. Heavy water inhibition of cell division: an approach to mechanism. Ann N Y Acad Sci 1960; 90:500-22.
- Takahashi TC, Sato H. Effects of heavy water (D2O) on the length of the mitotic period in developing sea urchin eggs. Cell Struct Funct 1983; 8(4):357-65.
- Soleyman-Jahi S, Zendehdel K, Akbarzadeh K, Haddadi M, Amanpour S, Muhammadnejad S. In vitro assessment of antineoplastic effects of deuterium depleted water. Asian Pac J Cancer Prev 2014; 15(5):2179-83.
- Bild W, Nastasa V, Haulica I. In vivo and in vitro research on the biological effects of deuterium-depleted water: 1. Influence of deuterium-depleted water on cultured cell growth. Rom J Physiol 2004; 41(1-2):53-67.
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