Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
권호 표지
DOI QR코드

DOI QR Code

Gefitinib Inhibits the Growth of Toxoplasma gondii in HeLa Cells

  • Yang, Zhaoshou (Department of Parasitology, College of Medicine, The Catholic University of Korea) ;
  • Ahn, Hye-Jin (Department of Parasitology, College of Medicine, The Catholic University of Korea) ;
  • Nam, Ho-Woo (Department of Parasitology, College of Medicine, The Catholic University of Korea)
  • Received : 2014.03.17
  • Accepted : 2014.06.24
  • Published : 2014.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Toxoplasma gondii is the causative agent of toxoplasmosis with symptoms of congenital neurological and ocular diseases and acquired lymphadenitis, retinochoroiditis, and meningoencephalitis. Small molecules which block the activity of protein kinases were tested in in vitro culture of T. gondii to find new therapeutic drugs of safer and more effective than the combined administration of pyrimethamine and sulfadoxine that sometimes provoke lethal Stevens-Johnson syndrome. Among them, Gefitinib and Crizotinib inhibited intracellular growth of T. gondii in HeLa cells by counting the number of T. gondii per parasitophorous vacuolar membrane whereas Sunitinib did not. Gefitinib inhibited the growth of T. gondii in a dose-dependent manner over $5{\mu}M$ up to the tolerable concentration of HeLa cells and halted the division of the parasite immediately from the time point of treatment. Gefitinib inhibition suggests that tyrosine kinases of EGFR family or other homologous kinases of the parasite itself may be the target to cause the block of T. gondii growth.

Keywords

References

  1. John DT, Petri WA (eds). The tissue coccidia: Toxoplasma gondii. Markell and Voge's Medical Parasitology (9th ed.). Elsevier Inc., USA. 2006, p 139-149.
  2. Choi WY, Nam HW, Kwak NH, Huh W, Kim YR, Kang MW, Cho SY. Foodborne outbreaks of human toxoplasmosis. J Infect Dis 1997; 175: 1280-1282. https://doi.org/10.1086/593702
  3. Park YH, Han JH, Nam HW. Clinical features of ocular toxoplasmosis in Korean patients. Korean J Parasitol 2011; 49: 157-171.
  4. Wei F, Wang W, Liu Q. Protein kinases of Toxoplasma gondii: functions and drug targets. Parasitol Res 2013; 112: 2121-2129. https://doi.org/10.1007/s00436-013-3451-y
  5. Qui W, Wernimont A, Tang K, Taylor S, Lunin V, Schapira M, Fentress S, Hui R, Sibley LD. Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii. EMBO J 2009; 28: 969-979. https://doi.org/10.1038/emboj.2009.24
  6. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nature Rev (Cancer) 2009; 9: 28-39. https://doi.org/10.1038/nrc2559
  7. Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G, Engelman JA, Ono M, Rho JK, Cascione L, Volinia S, Nephew KP, Croce CM. EGFR ad MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and Gefitinib resistance in lung cancers. Nature Med 2012; 18: 74-82.
  8. Cui JJ, Tran-Dube M, Shen H, Nambu M, Kung PP, Pairish M, Jia L, Meng J, Funk L, Botrous I, McTigue M, Grodsky N, Ryan K, Padrique E, Alton G, Timofeevski S, Yamazaki S, Li Q, Zou H, Christensen J, Mroczkowski B, Bender S, Kania RS, Edwards MP. Structure based drug design of Crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem 2011; 54: 6342-6363. https://doi.org/10.1021/jm2007613
  9. Stanley SA, Barczak AK, Silvis MR, Luo SS, Sogi K, Vokes M, Bray MA, Carpenter AE, Moore CB, Siddiqi N, Rubin EJ, Hung DT. Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth. PLoS Pathog 2014; 10: 1-16.

Cited by

  1. A Systematic Review of In vitro and In vivo Activities of Anti -Toxoplasma Drugs and Compounds (2006–2016) vol.8, pp.None, 2014, https://doi.org/10.3389/fmicb.2017.00025
  2. Activation of a Neospora caninum EGFR-Like Kinase Facilitates Intracellular Parasite Proliferation vol.8, pp.None, 2014, https://doi.org/10.3389/fmicb.2017.01980
  3. Suppressors for Human Epidermal Growth Factor Receptor 2/4 (HER2/4): A New Family of Anti-Toxoplasmic Agents in ARPE-19 Cells vol.55, pp.5, 2014, https://doi.org/10.3347/kjp.2017.55.5.491
  4. The Interplay of Host Autophagy and Eukaryotic Pathogens vol.6, pp.None, 2014, https://doi.org/10.3389/fcell.2018.00118
  5. Interplay Between Toxoplasma gondii , Autophagy, and Autophagy Proteins vol.9, pp.None, 2014, https://doi.org/10.3389/fcimb.2019.00139