Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis

  • Authors:
    • Feng-Song Cong
    • Ya-Ru Zhang
    • Hong-Cai Sheng
    • Zong-Hua Ao
    • Su-Yi Zhang
    • Ju-Yong Wang
  • View Affiliations

  • Published online on: March 1, 2010     https://doi.org/10.3892/etm_00000043
  • Pages: 277-283
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (DDW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72 h. Cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (MTT) proliferation assay. A549 cells were treated with 50±5 ppm DDW, and the morphology and structure of cells were observed by scanning electron microscopy (SEM). We observed alterations in the cellular skeleton by transmission electron microscopy (TEM) and changes in cell cycle by flow cytometry. Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under SEM and TEM. The length of the S phase increased significantly in cells treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were decreased. We observed DDW-induced cellular apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragment analyses. In addition, we established a tumor transplantion model by injecting H460 tumor cells into subcutaneous tissue of BALB/c mice treated with DDW for 60 days. We determined the tumor inhibition rate of treated and control groups and found that the tumor weight was significantly decreased and the tumor inhibition rate was approximately 30% in the DDW group. We conclude that DDW is a promising new anticancer agent with potential for future clinical application.

References

1. 

Carney DN: Lung cancer – time to move on from chemotherapy. N Engl J Med. 346:126–128. 2002.

2. 

Nishio K, Nakamura T, Koh Y, et al: Drug resistance in lung cancer. Curr Opin Oncol. 11:109–115. 1999. View Article : Google Scholar

3. 

Swisher S and Roth JA: Clinical update of Ad-p53 gene therapy for lung cancer. Surg Oncol Clin N Am. 11:521–535. 2002. View Article : Google Scholar : PubMed/NCBI

4. 

Criss RE: Principles of Stable Isotope Distribution. Oxford University Press; New York: pp. 234–1999

5. 

Collins CJ and Bowman NS: Isotope Effects in Chemical Reactions. Van Nostrand Reinhold; New York: pp. 286–363. 1971

6. 

Wiberg KB: The deuterium isotope effect. Chem Rev. 55:713–743. 1955. View Article : Google Scholar

7. 

Jancso G and van Hook WA: Condensed phase isotope effects: especially vapor pressure isotope effects. Chem Rev. 74:689–750. 1974. View Article : Google Scholar

8. 

Rundel PW, Ehleringer JR and Nagy KA: Stable Isotope in Ecological Research. Springer; New York: pp. 7–9. 1988

9. 

Hughes AM, Tolbert BM, Lonberg-Holm K, et al: The effect of deuterium oxide on survival of mice with ascites tumor. Biochim Biophys Acta. 28:58–61. 1958. View Article : Google Scholar : PubMed/NCBI

10. 

Laissue JA, Bally E, Joel DD, et al: Protection of mice from whole-body gamma radiation by deuteration of drinking water. Radiat Res. 96:59–64. 1983. View Article : Google Scholar : PubMed/NCBI

11. 

Gross PR and Spindel W: Heavy water inhibition of cell division: an approach to mechanism. Ann NY Acad Sci. 90:500–522. 1962. View Article : Google Scholar : PubMed/NCBI

12. 

Katz JJ, Crespi HL, Czajka DM, et al: Course of deuteriation and some physiological effects of deuterium in mice. Am J Physiol. 203:907–913. 1962.PubMed/NCBI

13. 

Katz JJ, Crespi HL and Hasterlik RJ: Some observations on biological effects of deuterium with special reference to effects on neoplastic processes. J Natl Cancer Inst. 18:641–659. 1957.PubMed/NCBI

14. 

Somlyai G, Jancsó G, Jákli G, et al: Naturally occurring deuterium is essential for the normal growth rate of cells. FEBS Lett. 317:1–4. 1993. View Article : Google Scholar : PubMed/NCBI

15. 

Siniak IuE, Turusov VS, Grigorev AI, et al: Consideration of the deuterium-free water supply to an expedition to Mars. Aviakosam Ekolog Med. 37:60–63. 2003.PubMed/NCBI

16. 

Turusov VS, Siniak IuE, Grigor’ev AI, et al: Low-deuterium water effect on transplantable tumors. Vopr Onkol. 51:99–102. 2005.PubMed/NCBI

17. 

Tyrysov VS, Siniak IuE, Antoshina EE, et al: The effect of preliminary administration of water with reduced deuterium content on the growth of transplantable tumors in mice. Vopr Onkol. 52:59–62. 2006.PubMed/NCBI

18. 

Somlyai G: Defeating cancer! The biological effect of deuterium depletion. Ramnicu Valcea, Romania Conphys. 60–61. 2001.

19. 

Laskay G, Somlyai G, Jancsó G, et al: Reduced deuterium concentration of water stimulates O2-uptake and electrogenic H+-efflux in the aquatic macrophyte Elodea canadensis. Jpn J Deuterim Sci. 10:17–23. 2001.

20. 

Berdea P, Cuna S, Cazacu M, et al: Deuterium variation of human blood serum. Studia Universitatis Babes-Bolyal, Physica. Special Issue. 256–258. 2001.

21. 

Gyongyi Z and Somlyai G: Deuterium depletion can decrease the expression of C-mys Ha-ras and p53 gene in carcinogen-treated mice. In Vivo. 14:437–440. 2000.PubMed/NCBI

Related Articles

Journal Cover

March 2010
Volume 1 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Cong, F., Zhang, Y., Sheng, H., Ao, Z., Zhang, S., & Wang, J. (2010). Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis . Experimental and Therapeutic Medicine, 1, 277-283. https://doi.org/10.3892/etm_00000043
MLA
Cong, F., Zhang, Y., Sheng, H., Ao, Z., Zhang, S., Wang, J."Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis ". Experimental and Therapeutic Medicine 1.2 (2010): 277-283.
Chicago
Cong, F., Zhang, Y., Sheng, H., Ao, Z., Zhang, S., Wang, J."Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis ". Experimental and Therapeutic Medicine 1, no. 2 (2010): 277-283. https://doi.org/10.3892/etm_00000043