Skip to main content
Log in

Inhibition of Mitochondrial Voltage-Dependent Anion Channels Increases Radiosensitivity of K562 Leukemic Cells

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of inhibition of mitochondrial voltage-dependent anion channels with DIDS on radiosensitivity and mitochondrial status of K562 leukemic cells. The number of apoptotic and necrotic cells, mitochondrial transmembrane potential, and mitochondrial mass were evaluated after irradiation of cells in doses of 4 and 12 Gy in the presence and absence of the inhibitor. Inhibition of mitochondrial voltage-dependent anion channels increased radiosensitivity of K562 cells by 50-70% and decreased both mitochondrial transmembrane potential and mitochondrial mass. Inhibitors of voltage-dependent anion channels are promising agents capable of improving the effectiveness of cancer radiotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. A. Cossarizza, G. Kalashnikova, E. Grassilli, F. Chiappelli, S. Salvioli, M. Capri, D. Barbieri, L. Troiano, D. Monti, and C. Franceschi, Mitochondrial modifications during rat thymocyte apoptosis: a study at the single cell level. Exp. Cell Res., 214, No. 1, 323–330 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Z. Gan, S. H. Audi, R. D. Bongard, K. M. Gauthier, and M. P. Merker, Quantifying mitochondrial and plasma membrane potentials in intact pulmonary arterial endothelial cells based on extracellular disposition of rhodamine dyes. Am. J. Physiol. Lung Cell. Mol. Physiol., 300, No. 5, L762-L772 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. D. Han, F. Antunes, R. Canali, D. Rettori, and E. Cadenas, Voltage-dependent anion channels control the release of the superoxide anion from mitochondria to cytosol. J. Biol. Chem., 278, No. 8, 5557–5563 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. J. A. Hannay, J. Liu, Q. S. Zhu, S. V. Bolshakov, L. Li, P. W. Pisters, A. J. Lazar, D. Yu, R. E. Pollock, and D. Lev, Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation. Mol. Cancer. Ther., 6, No. 5, 1650–1660 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. T. Himi, Y. Ishizaki, and S. I. Murota, 4,4’-Diisothiocyano- 2,2’-stilbenedisulfonate protects cultured cerebellar granule neurons from death. Life Sci., 70, No. 11, 1235–1249 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. M. Huizing, W. Ruitenbeek, L. P. van den Heuvel, V. Dolce, V. Iacobazzi, J. A. Smeitink, F. Palmieri, and J. M. Trijbels, Human mitochondrial transmembrane metabolite carriers: tissue distribution and its implication for mitochondrial disorders, J. Bioenerg. Biomembr., 30, No. 3, 277–284 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. T. Ishida, Y. Takizawa, T. Kainuma, J. Inoue, T. Mikawa, T. Shibata, H. Suzuki, S. Tashiro, and H. Kurumizaka, DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange. Nucleic Acids Res., 37, No. 10, 3367–3376 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. K. R. Lamont, M. G. Hasham, N. M. Donghia, J. Branca, M. Chavaree, B. Chase, A. Breggia, J. Hedlund, I. Emery, F. Cavallo, M. Jasin, J. Rüter, and K. D. Mills, Attenuating homologous recombination stimulates an AID-induced antileukemic effect. J. Exp. Med., 210, No. 5, 1021–1033 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. K. Mizoguchi, H. Maeta, A. Yamamoto, M. Oe, and H. Kosaka, Amelioration of myocardial global ischemia/reperfusion injury with volume-regulatory chloride channel inhibitors in vivo. Transplantation, 73, No. 8, 1185–1193 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. E. Nozik-Grayck, C. A. Piantadosi, J. van Adelsberg, S. L. Alper, and Y. Huang, Protection of perfused lung from oxidant injury by inhibitors of anion exchange. Am. J. Physiol., 273, No. 2, Pt 1, L296-L304 (1997).

  11. Y. Saenko, A. Cieslar-Pobuda, M. Skonieczna, and J. Rzeszowska- Wolny, Changes of reactive oxygen and nitrogen species and mitochondrial functioning in human K562 and HL60 cells exposed to ionizing radiation. Radiat. Res., 180, No. 4, 360–366 (2013).

  12. J. M. Sage, O. S. Gildemeister, and K. L. Knight, Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome. J. Biol. Chem., 285, No. 25, 18,984-18,990 (2010).

    Article  CAS  Google Scholar 

  13. V. Shoshan-Barmatz, D. Mizrachi, and N. Keinan, Oligomerization of the mitochondrial protein VDAC1: from structure to function and cancer therapy. Prog. Mol. Biol. Transl. Sci., 117, 303–334 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, and C. P. Reutelingsperger, Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry, 31, No. 1, 1–9 (1998).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Y. V. Saenko.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 161, No. 1, pp. 119–123, January, 2016

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saenko, Y.V., Mastilenko, A.V., Glushchenko, E.S. et al. Inhibition of Mitochondrial Voltage-Dependent Anion Channels Increases Radiosensitivity of K562 Leukemic Cells. Bull Exp Biol Med 161, 104–107 (2016). https://doi.org/10.1007/s10517-016-3356-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-016-3356-8

Key Words

Navigation