Advertisement

Bulletin of Experimental Biology and Medicine

, Volume 166, Issue 5, pp 646–650 | Cite as

Synthetic Phenolic Antioxidant TS-13 Suppresses the Growth of Lewis Lung Carcinoma and Potentiates Oncolytic Effect of Doxorubicin

  • E. B. Men’shchikovaEmail author
  • N. K. Zenkov
  • P. M. Kozhin
  • A. V. Chechushkov
  • A. V. Kovner
  • M. V. Khrapova
  • N. V. Kandalintseva
  • G. G. Martinovich
ONCOLOGY
  • 6 Downloads

ROS are important intracellular messengers; their ambiguous role in malignant processes was demonstrated in many studies. The effects of a synthetic phenolic antioxidant sodium 3-(3’-tert-butyl-4’-hydroxyphenyl)propyl thiosulfonate sodium (TS-13) on the tumor growth and oncolytic properties of doxorubicin were studied in the experimental model of Lewis lung carcinoma in mice. In mice receiving TS-13 with drinking water (100 mg/kg), suppression of tumor growth by 32.3% was observed on day 21 after inoculation of Lewis lung carcinoma cells. Two-fold intraperitoneal injections of doxorubicin in a cumulative dose of 8 mg/kg were followed by inhibition of tumor growth by 49.5%. Combined treatment with TS-13 and doxorubicin suppressed the tumor growth by 55.4%. In contrast to doxorubicin, TS-13 inhibited NO generation by peritoneal macrophages. The results show the prospect of studying TS-13 in the context of overcoming drug-resistance of tumors.

Key Words

reactive oxygen metabolites grafted Leis lung carcinoma sulphur-containing phenolic antioxidant TS-13 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bogatyrenko TN, Sashenkova TE, Mishchenko DV, Kandalintseva NV. Sulfur-containing phenolic antioxidants increasing antitumor efficiency of cyclophosphamide and its combination with nitric oxide donor. Rus. Chem. Bull. 2018;67(4):700-704.CrossRefGoogle Scholar
  2. 2.
    Zenkov NK, Kozhin PM, Chechushkov AV, Menshchikova EB, Martinovich GG, Kandalintseva NV. Mazes of Nrf2 regulation. Biochemistry (Moscow). 2017;82(5):556-564.CrossRefGoogle Scholar
  3. 3.
    Zenkov NK, Menshchikova EB, Kandalintseva NV, Oleynik AS, Prosenko AE, Gusachenko ON, Shklyaeva OA, Vavilin VA, Lyakhovich VV. Antioxidant and antiinflammatory activity of new water-soluble sulfur-containing phenolic compounds. Biochemistry (Moscow). 2007;72(6):644-651.CrossRefGoogle Scholar
  4. 4.
    Martinovich GG, Martinovich IV, Vcherashniaya AV, Zenkov NK, Cherenkevich SN, Menshchikova EB, Kandalintseva NV. Mechanisms of Redox Regulation of Chemoresistance in Tumor Cells by Phenolic Antioxidants. Biophysics. 2017;62(6):942-949.CrossRefGoogle Scholar
  5. 5.
    Martinovich GG, Martinovich IV, Cherenkevich SN, Zenkov NK, Menshchikova EB, Kandalintseva NV. Phenolic antioxidant TS-13 regulating ARE-driven genes induces tumor cell death by a mitochondria-dependent pathway. Biophysics. 2015;60(1):94-100.CrossRefGoogle Scholar
  6. 6.
    Menshchikova EB, Tkachev VO, Zenkov NK, Lemza AE, Sharkova TV, Kandalintseva NV. Anti-inflammatory activity of TS-13, ARE-inducing phenol antioxidant. Bull. Exp. Biol. Med. 2013;155(3):366-369.CrossRefGoogle Scholar
  7. 7.
    Anantharaju PG, Gowda PC, Vimalambike MG, Madhunapantula S.V. An overview on the role of dietary phenolics for the treatment of cancers. Nutr. J. 2016;15(1):99.CrossRefGoogle Scholar
  8. 8.
    Dinkova-Kostova AT, Fahey JW, Kostov RV, Kensler TW. KEAP1 and done? Targeting the NRF2 pathway with sulforaphane. Trends Food Sci. Technol. 2017;69(Pt B):257-269.CrossRefGoogle Scholar
  9. 9.
    Kitamura H, Motohashi H. NRF2 addiction in cancer cells. Cancer Sci. 2018;109(4):900-911.CrossRefGoogle Scholar
  10. 10.
    Kumari S, Badana AK, Gavara MM, Gugavalath S, Malla R. Reactive oxygen species: a key constituent in cancer survival. Biomark. Insights. 2018;13. ID 1177271918755391. doi:  https://doi.org/10.1177/1177271918755391.
  11. 11.
    Lok HC, Sahni S, Jansson PJ, Kovacevic Z, Hawkins CL, Richardson DR. A nitric oxide storage and transport system that protects activated macrophages from endogenous nitric oxide cytotoxicity. J. Biol. Chem. 2016;291(53):27,042-27,061.CrossRefGoogle Scholar
  12. 12.
    Onishi H, Fukasawa A, Miatmoko A, Kawano K, Ikeuchi-Takahashi Y, Hattori Y. Preparation of chondroitin sulfateadipic acid dihydrazide-doxorubicin conjugate and its antitumour characteristics against LLC cells. J. Drug Target. 2017;25(8):747-753.CrossRefGoogle Scholar
  13. 13.
    Rahat MA, Hemmerlein B. Macrophage-tumor cell interactions regulate the function of nitric oxide. Front. Physiol. 2013;4:144. doi:  https://doi.org/10.3389/fphys.2013.00144.CrossRefGoogle Scholar
  14. 14.
    Rajagopal C, Lankadasari MB, Aranjani JM, Harikumar KB. Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy. Pharmacol. Res. 2018;130:273-291.CrossRefGoogle Scholar
  15. 15.
    Russo GL, Tedesco I, Spagnuolo C, Russo M. Antioxidant polyphenols in cancer treatment: Friend, foe or foil? Semin. Cancer Biol. 2017;46:1-13.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • E. B. Men’shchikova
    • 1
    Email author
  • N. K. Zenkov
    • 1
  • P. M. Kozhin
    • 1
  • A. V. Chechushkov
    • 1
  • A. V. Kovner
    • 1
  • M. V. Khrapova
    • 1
  • N. V. Kandalintseva
    • 2
  • G. G. Martinovich
    • 3
  1. 1.Federal Research Center of Fundamental and Translational MedicineNovosibirskRussia
  2. 2.Novosibirsk State Pedagogical UniversityNovosibirskRussia
  3. 3.Belarusian State UniversityMinskRepublic of Belarus

Personalised recommendations