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Induction of Oxidative Stress in Tumor Cells: A New Strategy for Drug Therapy of Malignant Tumors

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Abstract—Tumor cells have a higher basal ROS level than normal cells. This phenomenon may provide grounds for the development of novel antitumor drugs that are capable of selectively inducing oxidative stress in tumor cells. This approach can involve agents that induce ROS production and/or inhibit cellular enzymatic antioxidant systems. Thioredoxin reductase is a key enzyme in such systems. Overexpression of thioredoxin reductase has been shown in several types of tumors of hematopoietic, lymphoid, and other tissues. The results of studies of the antitumor activities of various synthetic and natural substances that are able to inhibit thioredoxin reductase are summarized. It is shown that thioredoxin reductase inhibition results in an increase in ROS level in tumor cells and oxidative damage of cells followed by apoptosis mainly via the mitochondrial pathway.

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REFERENCES

  1. D. Trachootham, J. Alexandre, and P. Huang, Nature Rev. Drug Discov. 8, 579 (2009).

    Article  Google Scholar 

  2. S. Galadary, A. Rahman, A. Palliehakandys, and F. Thayyullathie, Free Radic. Biol. Med. 104, 144 (2017).

    Article  Google Scholar 

  3. D. B. Zurov, M. Yuhaszova, and S. J. Sollett, Biochem. Biophys. Acta 1757, 509 (2006).

    Google Scholar 

  4. B. R. You, H. R. Shiu, B. R. Han, and W. H. Park, Tumor Biol. 3, 2087 (2015).

    Article  Google Scholar 

  5. C. Gorrinia, I. S. Harris, and T. W. Mak, Nature Rev. Drug Discov. 12, 931(2013).

    Article  Google Scholar 

  6. D. B. Korman, Prakt, Onkol. 11 (2), 76 (2011).

    Google Scholar 

  7. A. J. Montero and J. Jassem, Drugs 71, 1385 (2011).

    Article  Google Scholar 

  8. P. Koedrith and Y. R. Seo, Exp. Ther. Med. 8, 873 (2011).

    Article  Google Scholar 

  9. R. Marulle, E. Werner, N. Degtuarena, et al., PloS One, 8 (II), e81162m (2013). https://doi.org/10.1371/jornal.pone.0081162

    Article  ADS  Google Scholar 

  10. D. B. Korman, Antitumor Drugs: Targets and Mechanisms of Action (Prakticheskaya Meditsina, Moscow, 2014) [in Russian].

    Google Scholar 

  11. I. N. Todorov and G. I. Todorov, Stress, Senescence, and Their Biochemical Correction (Nauka, Moscow, 2003) [in Russian].

    Google Scholar 

  12. C. Fan, X. Fu, Z. Zhang, et al., Sci. Rep. 7, 6455 (2017). https://doi.org/10.1038/s41598-017-06979-2

    Article  ADS  Google Scholar 

  13. J. R. Kirshner, S. He, V. Balasubramahyam, and J. Kepros, Mol. Cancer Ther. 7 (8), 2319 (2008).

    Article  Google Scholar 

  14. S. O’Day, R. Gonzalez, D. Lawson, et al., J. Clin. Oncol. 32, 5452 (2009).

    Article  Google Scholar 

  15. S. J. O`Day, A. M. Eggermont, V. Chiariasileni, et al., J. Clin. Oncol. 3, 1211 (2013).

    Article  Google Scholar 

  16. D. Magda and R. A. Miller, Semin. Cancer Biol. 16, 466 (2006).

    Article  Google Scholar 

  17. E. S. Arner and A. Holmgren, Semin. Oncol. 16, 420, (2006).

    Google Scholar 

  18. A. Holmgren and J. Lu, Biochem. Biophys. Res. Com. 396, 120 (2010).

    Article  Google Scholar 

  19. S. Lee, S. M. Kim, and R. T. Lee, Antioxid Redox Signal. 18, 1165 (2013).

    Article  Google Scholar 

  20. F. Saccocia, F. Angelucci, G. Boumis, et al., Curr. Prot. Pept. Sci. 15, 621 (2014).

    Article  Google Scholar 

  21. J. Zhang, Y. Lin, D. Shi, et al., Eur. J. Med. Chem. 140, 435 (2017).

    Article  Google Scholar 

  22. M. Beggren, A. Gallegos, J. R. Gasdaska, et al., Antcancer Res. 16, 3459 (1996).

    Google Scholar 

  23. S. Kakolyris, A. Giatromanolaki, M. Konkourakis, et al., Clin. Cancer Res. 7, 3087 (2001).

    Google Scholar 

  24. B. R. You, H. R. Shiu, B. R. Han, W. H. Park, Tumor Biol. 3, 2087 (2015).

    Article  Google Scholar 

  25. D. Duan, J. Zhang, J. Jao, et al., J. Biol. Chem. 291, 10021 (2016).

    Article  Google Scholar 

  26. W. C. Stafford, X. Peng, M. H. Olofsson, et al., Sci. Transl. Med. 10, 428 (2018). https://doi.org/10.1126/scitransmed.aaf7444

    Article  Google Scholar 

  27. J. Lu and A. Holmgren, Free Radic. Biol. Med. 66, 75 (2014).

    Article  Google Scholar 

  28. M. Gebula, E. E. Scmidt, and E. S. Arner, Antioxid. Redox Signal. 23, 823 (2015).

    Article  Google Scholar 

  29. A. Matsuzawa, Arch. Biochem. Bioph. 617, 101 (2017).

    Article  Google Scholar 

  30. A. Bindoli, M. P. Rigobello, G. Scurari, et al., Coordination Chem. Rev. 253, 1692 (2009).

    Article  Google Scholar 

  31. F. Y. Zhao, Z. Y. Du, D. L. Ma, et al., Oncotarget 6, 30939 (2015).

    Google Scholar 

  32. S. Urig and K. Becker, Sem. Cancer Biol. 16, 452 (2006).

    Article  Google Scholar 

  33. A. F. Baker, K. N. Adab, N. Raghunand, et al., Invest. New Drugs 31, 631 (2013).

    Article  Google Scholar 

  34. J. Zhang, S. Peng, X. Li, et al., Arch. Biochem. Biophys. 16, 16 (2017).

    Article  Google Scholar 

  35. A. P. Fernandes, A. Capitano, M. Selenius, et al., Histopathology 55, 313 (2009).

    Article  Google Scholar 

  36. M. Wangpaichitr and E. J. Sullivan, Mol. Cancer Ther. 11, 604 (2011).

    Article  Google Scholar 

  37. J. Y. Lim, S. O. Yoon, and S. W. Heng, Word Gastroenterol. 18, 55 (2012).

    Article  ADS  Google Scholar 

  38. M. K. Cha, K. H. Suh, and L. N. Kim, J. Exp. Clin. Cancer Res. 28, 93 (2009).

    Article  Google Scholar 

  39. D. T. Lincoln, F. Al-Yatama, F. M. Mohammed, et al., Anticancer Res. 30, 767 (2010).

    Google Scholar 

  40. Y. Cheng and Y. Qi, Anticancer Agents Med. Chem. 17, 1046 (2017).

    Article  Google Scholar 

  41. M. H. Yoo, X. M. Xu, B. A. Carison, et al., J. Biol. Chem. 261, 13005 (2006).

    Article  Google Scholar 

  42. H. R. Shin, B. R. You, and W. H. Park, Oncol. Lett. 1804 (2013).

  43. S. J. Welsh, R. Willias, A. Bermingham, et al., Mol. Cancer Ther. 3, 235 (2003).

    Google Scholar 

  44. R. K. Ramanathan, J. Abbruzzese, T. Dragovich, et al., Cancer Chemother. Pharmacol. 67, 503 (2011).

    Article  Google Scholar 

  45. W. Cai, L. Zhang, Y. Song, et al., Free Rad. Biol. Med. 52, 257 (2012).

    Article  Google Scholar 

  46. Y. Liu, Y. Li, S. Yu, and G. Zhao, Curr. Drug Targets 13, 1432 (2012).

    Article  Google Scholar 

  47. D. Saggioro, M. P. Rigobello, L. Paloschi, et al., Chem. Biol. 14, 1128 (2007).

    Article  Google Scholar 

  48. E. Topkas, N. Cai, and A. Cumming, Oncotarget 7, 831 (2016).

    Article  Google Scholar 

  49. V. Gandin, A. P. Fernandes, M. P. Rigobello, Biochem. Pharmacol. 78, 90 (2010).

    Article  Google Scholar 

  50. L. Bu, W. Li, Z. Ming, et al., Life Sci. 178, 35 (2017).

    Article  Google Scholar 

  51. L. Lan, F. Zhoa, Y. Wang, and H. Zeng, Eur. J. Pharmacol. 555, 83 (2007).

    Article  Google Scholar 

  52. L. A. Ostrovskaya, M. G. Voronkov, D. B. Korman, et al., Biophysics (Moscow) 59 (4), 642 (2014).

    Article  Google Scholar 

  53. L. A. Ostrovskaya, D. B. Korman, N. V. Bluhterova, et al., Biointerface Res. Appl. Chem. 4 (4), 816 (2014).

    Google Scholar 

  54. L. A. Ostrovskaya, D. B. Korman, A. K. Grekhova, et al., Izv. Akad. Nauk, Ser. Khim., No. 12, 2333 (2017).

  55. C. Nardon, G. Boscutti, and D. Fregona, Anticancer Res. 34, 487 (2014).

    Google Scholar 

  56. Z. F. Peng, L. X. Lan, F. Zhao, et al., J. Zhejiang Univ. Sci. B. 9, 16 (2008).

    Article  Google Scholar 

  57. Y. W. Liang, J. Zheng, X. Li, et al., Eur. J. Med. Chem. 84, 335 (2014).

    Article  Google Scholar 

  58. X. Zheng, W. Ma, R. Sun, et al., Redox Biol. 14, 237 (2018).

    Article  Google Scholar 

  59. C. Fan, W. Zheng, and X. Fu, Cell Death Dis. 5, 191 (2014).

  60. S. Bronzmanova, D. Manikova, V. Vickova, and M. Chovanee, Arch. Toxicol. 84, 919 (2010).

    Article  Google Scholar 

  61. W. Wang, Meng, Z. Wang, et al., Cell Biol. Int. 42, 580 (2018).

    Article  Google Scholar 

  62. F. Y. Zhao, S. Wang, H. Y. Li, et al., Oncotarget 7, 6791 (2016).

    Google Scholar 

  63. J. Lu, L. V. Papp, J. Fang, et al., Cancer Res. 66, 4410 (2006).

    Article  Google Scholar 

  64. G. H. Hwang, J. M. Ryu, and Y. J. Jeon, Eur. L. Pharmacol. 765, 384 (2015).

    Article  Google Scholar 

  65. H. Huang, H. Xie, Y. Pan, et al., Cell Physiol. Biochem. 45, 267 (2018).

    Article  Google Scholar 

  66. A. Kawiak, J. Piosik, G. Stasilojc, et al., Toxicol. Appl. Pharmacol. 223, 867 (2007).

    Article  Google Scholar 

  67. C. Yan, D. Sigel, J. Newsome, et al., Mol. Pharmacol. 81, 401 (2012).

    Article  Google Scholar 

  68. K. K. Kaminska, H. C. Bertrand, H. Tajima, et al., Oncotarget 7, 40233 (2016).

    Article  Google Scholar 

  69. T. Rajavel, P. Packiyarai, and V. Suryanarayanan, Sci. Rep. 8, 2071 (2018).

    Article  ADS  Google Scholar 

  70. Auranofin and Sirolimus in Treating Participants with Ovarian Cancer. https://clinicaltrials.gov/ct2/ show/NCT03456700.

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FUNDING

This work was supported by the Russian Federation Ministry of Education and Science, Federal Targeted Program Research and Development in the Priority Areas of the Russian Science and Technology Sector for 2014–2020 (Agreement 14.607.21.0199 of September 26, 2017 Development of the Technology for the Preparation of a Medicine Based on Nanostructured Gold Polyacrylate for Molecularly Targeted Tumor Treatment).

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Authors and Affiliations

  1. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334, Moscow, Russia

    D. B. Korman, L. A. Ostrovskaya & V. A. Kuz’min

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  1. D. B. Korman
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  2. L. A. Ostrovskaya
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  3. V. A. Kuz’min
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Correspondence to D. B. Korman.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Translated by Victor Gulevich

Abbreviations: ROS, reactive oxygen species; NSCLC, non-small-cell lung carcinoma; Trx, thioredoxin; TrxR, thioredoxin reductase; shRNA, short hairpin RNA.

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Korman, D.B., Ostrovskaya, L.A. & Kuz’min, V.A. Induction of Oxidative Stress in Tumor Cells: A New Strategy for Drug Therapy of Malignant Tumors. BIOPHYSICS 64, 431–439 (2019). https://doi.org/10.1134/S0006350919030102

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