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References

  1. Atroshi F, Rizzo A, Westermarck T, Ali-Vehmas T. 1998. Effects of tamoxifen, melatonin, coenzyme Q10, and L-carnitine supplementation on bacterial growth in the presence of mycotoxins. Pharmacol. Res. 38: 289-295.
    Pubmed CrossRef
  2. Caleffi-Ferracioli KR, Maltempe FG, Siqueira VL, Cardoso RF. 2013. Fast detection of drug interaction in Mycobacterium tuberculosis by a checkerboard resazurin method. Tuberculosis (Edinb.) 93: 660-663.
    Pubmed CrossRef
  3. Changsen C, Franzblau SG, Palittapongarnpim P. 2003. Improved green fluorescent protein reporter gene-based microplate screening for antituberculosis compounds by utilizing an acetamidase promoter. Antimicrob. Agents Chemother. 47: 3682-3687.
    Pubmed PMC CrossRef
  4. Chen FC, Liao YC, Huang JM, Lin CH, Chen YY, Dou HY, Hsiung CA. 2014. Pros and cons of the tuberculosis drugome approach - an empirical analysis. PLoS One 9: e100829.
    Pubmed PMC CrossRef
  5. Christophe T, Jackson M, Jeon HK, Fenistein D, ContrerasDominguez M, Kim J, et al. 2009. High content screening identifies decaprenyl-phosphoribose 2’ epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 5:e1000645.
    Pubmed PMC CrossRef
  6. Dolan K, Montgomery S, Buchheit B, Didone L, Wellington M, Krysan DJ. 2009. Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization. Antimicrob. Agents Chemother. 53: 3337-3346.
    Pubmed PMC CrossRef
  7. El Arbi M, Théolier J, Pigeon P, Jellali K, Trigui F, Top S, et al. 2014. Antibacterial properties and mode of action of new triaryl butene citrate compounds. Eur. J. Med. Chem. 76: 408-413.
    Pubmed CrossRef
  8. Jayachandran R, Scherr N, Pieters J. 2012. Elimination of intracellularly residing Mycobacterium tuberculosis through targeting of host and bacterial signaling mechanisms. Expert Rev. Anti Infect. Ther. 10: 1007-1022.
    Pubmed CrossRef
  9. Kaufmann SHE. 2001. How can immunology contribute to the control of tuberculosis? Nat. Rev. Immunol. 1: 20-30.
    Pubmed CrossRef
  10. Luxo C, Jurado AS, Madeira VM, Silva MT. 2003. Tamoxifen induces ultrastructural alterations in membranes of Bacillus stearothermophilus. Toxicol. Vitol. 17: 623-628.
    CrossRef
  11. Luo X, Pires D, Ainsa JA, Gracia B, Mulhovo S, Duarte A, et al. 2011. Antimycobacterial evaluation and preliminary phytochemical investigation of selected medicinal plants traditionally used in Mozambique. J. Ethnopharmacol. 137: 114-120.
    Pubmed CrossRef
  12. Miguel DC, Zauli-Nascimento RC, Yokoyama-Yasunaka JK, Katz S, Barbieri CL, Uliana SR. 2009. Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections. J. Antimicrob. Chemother. 63: 365-368.
    Pubmed CrossRef
  13. Naik SK, Mohanty S, Padhi A, Pati R, Sonawane A. 2014. Evaluation of antibacterial and cytotoxic activity of Artemisia nilagirica and Murraya koenigii leaf extracts against mycobacteria and macrophages. BMC Complement. Altern. Med. 14: 87.
    Pubmed PMC CrossRef
  14. Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. 2002. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 46:2720-2722.
    Pubmed PMC CrossRef
  15. Pecora ND, Fulton SA, Reba SM, Drage MG, Simmons DP, Urankar-Nagy NJ, et al. 2009. Mycobacterium bovis BCG decreases MHC-II expression in vivo on murine lung macrophages and dendritic cells during aerosol infection. Cell Immunol. 254: 94-104.
    Pubmed PMC CrossRef
  16. Singh R, Hussain S, Verma R, Sharma P. 2013. Antimycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica. Asian Pac. J. Trop. Med. 6: 366-371.
    CrossRef
  17. Vandal OH, Nathan CF, Ehrt S. 2009. Acid resistance in Mycobacterium tuberculosis. J. Bacteriol. 191: 4714-4721.
    Pubmed PMC CrossRef
  18. Vandal OH, Pierini LM, Schnappinger D, Nathan CF, Ehrt S. 2008. A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis. Nat. Med. 14:849-854.
    Pubmed PMC CrossRef

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Article

Note

J. Microbiol. Biotechnol. 2015; 25(6): 946-950

Published online June 28, 2015 https://doi.org/10.4014/jmb.1412.12023

Copyright © The Korean Society for Microbiology and Biotechnology.

Anti-Mycobacterial Activity of Tamoxifen Against Drug-Resistant and Intra-Macrophage Mycobacterium tuberculosis

Woong Sik Jang 1, Sukyung Kim 2, Biswajit Podder 2, Md. Anirban Jyoti 2, Kung-Woo Nam 3, Byung-Eui Lee 4 and Ho-Yeon Song 1, 2*

1Regional Innovation Center, Soonchunhyang University, Asan 336-745, Republic of Korea, 2Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea, 3Departments of Life Science and Biotechnology Soonchunhyang University, Asan 336-745, Republic of Korea, 4Department of Chemistry, Soonchunhyang University, Asan 336-745, Republic of Korea

Received: December 10, 2014; Accepted: January 22, 2015

Abstract

Recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis
drugs because of the increasing emergence of multidrug-resistant (MDR)
tuberculosis and extensively drug-resistant (XDR) tuberculosis. We evaluated here the antimycobacterial
activity of tamoxifen, known as a synthetic anti-estrogen, against eight drugsensitive
or resistant strains of Mycobacterium tuberculosis (TB), and the active intracellular
killing of tamoxifen on TB in macrophages. The results showed that tamoxifen had antituberculosis
activity against drug-sensitive strains (MIC, 3.125-6.25 μg/ml) as well as drugresistant
strains (MIC, 6.25 to 12.5 μg/ml). In addition, tamoxifen profoundly decreased the
number of intracellular TB in macrophages in a dose-dependent manner.

Keywords: Mycobacterium tuberculosis, Tamoxifen, Intracellular killing, MDR, XDR

References

  1. Atroshi F, Rizzo A, Westermarck T, Ali-Vehmas T. 1998. Effects of tamoxifen, melatonin, coenzyme Q10, and L-carnitine supplementation on bacterial growth in the presence of mycotoxins. Pharmacol. Res. 38: 289-295.
    Pubmed CrossRef
  2. Caleffi-Ferracioli KR, Maltempe FG, Siqueira VL, Cardoso RF. 2013. Fast detection of drug interaction in Mycobacterium tuberculosis by a checkerboard resazurin method. Tuberculosis (Edinb.) 93: 660-663.
    Pubmed CrossRef
  3. Changsen C, Franzblau SG, Palittapongarnpim P. 2003. Improved green fluorescent protein reporter gene-based microplate screening for antituberculosis compounds by utilizing an acetamidase promoter. Antimicrob. Agents Chemother. 47: 3682-3687.
    Pubmed KoreaMed CrossRef
  4. Chen FC, Liao YC, Huang JM, Lin CH, Chen YY, Dou HY, Hsiung CA. 2014. Pros and cons of the tuberculosis drugome approach - an empirical analysis. PLoS One 9: e100829.
    Pubmed KoreaMed CrossRef
  5. Christophe T, Jackson M, Jeon HK, Fenistein D, ContrerasDominguez M, Kim J, et al. 2009. High content screening identifies decaprenyl-phosphoribose 2’ epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 5:e1000645.
    Pubmed KoreaMed CrossRef
  6. Dolan K, Montgomery S, Buchheit B, Didone L, Wellington M, Krysan DJ. 2009. Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization. Antimicrob. Agents Chemother. 53: 3337-3346.
    Pubmed KoreaMed CrossRef
  7. El Arbi M, Théolier J, Pigeon P, Jellali K, Trigui F, Top S, et al. 2014. Antibacterial properties and mode of action of new triaryl butene citrate compounds. Eur. J. Med. Chem. 76: 408-413.
    Pubmed CrossRef
  8. Jayachandran R, Scherr N, Pieters J. 2012. Elimination of intracellularly residing Mycobacterium tuberculosis through targeting of host and bacterial signaling mechanisms. Expert Rev. Anti Infect. Ther. 10: 1007-1022.
    Pubmed CrossRef
  9. Kaufmann SHE. 2001. How can immunology contribute to the control of tuberculosis? Nat. Rev. Immunol. 1: 20-30.
    Pubmed CrossRef
  10. Luxo C, Jurado AS, Madeira VM, Silva MT. 2003. Tamoxifen induces ultrastructural alterations in membranes of Bacillus stearothermophilus. Toxicol. Vitol. 17: 623-628.
    CrossRef
  11. Luo X, Pires D, Ainsa JA, Gracia B, Mulhovo S, Duarte A, et al. 2011. Antimycobacterial evaluation and preliminary phytochemical investigation of selected medicinal plants traditionally used in Mozambique. J. Ethnopharmacol. 137: 114-120.
    Pubmed CrossRef
  12. Miguel DC, Zauli-Nascimento RC, Yokoyama-Yasunaka JK, Katz S, Barbieri CL, Uliana SR. 2009. Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections. J. Antimicrob. Chemother. 63: 365-368.
    Pubmed CrossRef
  13. Naik SK, Mohanty S, Padhi A, Pati R, Sonawane A. 2014. Evaluation of antibacterial and cytotoxic activity of Artemisia nilagirica and Murraya koenigii leaf extracts against mycobacteria and macrophages. BMC Complement. Altern. Med. 14: 87.
    Pubmed KoreaMed CrossRef
  14. Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. 2002. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 46:2720-2722.
    Pubmed KoreaMed CrossRef
  15. Pecora ND, Fulton SA, Reba SM, Drage MG, Simmons DP, Urankar-Nagy NJ, et al. 2009. Mycobacterium bovis BCG decreases MHC-II expression in vivo on murine lung macrophages and dendritic cells during aerosol infection. Cell Immunol. 254: 94-104.
    Pubmed KoreaMed CrossRef
  16. Singh R, Hussain S, Verma R, Sharma P. 2013. Antimycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica. Asian Pac. J. Trop. Med. 6: 366-371.
    CrossRef
  17. Vandal OH, Nathan CF, Ehrt S. 2009. Acid resistance in Mycobacterium tuberculosis. J. Bacteriol. 191: 4714-4721.
    Pubmed KoreaMed CrossRef
  18. Vandal OH, Pierini LM, Schnappinger D, Nathan CF, Ehrt S. 2008. A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis. Nat. Med. 14:849-854.
    Pubmed KoreaMed CrossRef