DOI QR코드

DOI QR Code

Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells

  • Hwang, Narae (Department of Biological Sciences, University of Ulsan) ;
  • Chung, Su Wol (Department of Biological Sciences, University of Ulsan)
  • 투고 : 2020.02.20
  • 심사 : 2020.04.10
  • 발행 : 2020.05.31

초록

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

키워드

참고문헌

  1. Xiong R, Zhao J, Gutgesell LM et al (2017) Novel SERDs Developed against treatment-resistant breast cancer. J Med Chem 60, 1325-1342 https://doi.org/10.1021/acs.jmedchem.6b01355
  2. Yang G, Nowsheen S, Aziz K and Georgakilas AG (2013) Toxicity and adverse effects of tamoxifen and other anti-estrogen drugs. Pharmacol Ther 139, 392-404 https://doi.org/10.1016/j.pharmthera.2013.05.005
  3. Wang L, Miao H and Li X (2015) Tamoxifen retinopathy: a case report. Springerplus 4, 501 https://doi.org/10.1186/s40064-015-1258-2
  4. Kim LA, Amarnani D, Gnanaguru G et al (2014) Tamoxifen toxicity in cultured RPE cells is mediated by concurrent regulated cell death mechanisms. Invest Ophthalmol Vis Sci 55, 4747-4758 https://doi.org/10.1167/iovs.13-13662
  5. Koulisis N, Moysidis SN, Olmos de Koo LC et al (2016) The tipping point: Tamoxifen toxicity, central serous chorioretinopathy, and the role of estrogen and its receptors. Am J Ophthalmol Case Rep 3, 8-13 https://doi.org/10.1016/j.ajoc.2016.05.004
  6. Abdollahzadeh I, Hendriks J, Sanwald JL et al (2019) Autophagy-related proteins GABARAP and LC3B label structures of similar size but different shape in superresolution imaging. Molecules 24, 1833 https://doi.org/10.3390/molecules24091833
  7. Uchiyama Y, Shibata M, Koike M et al (2008) Autophagyphysiology and pathophysiology. Histochem Cell Biol 129, 407-420 https://doi.org/10.1007/s00418-008-0406-y
  8. Bergsbaken T, Fink SL and Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7, 99-109 https://doi.org/10.1038/nrmicro2070
  9. Kummerle-Deschner J and Dannecker G (1995) Sulphasalazine desensitization in a paediatric patient with juvenile chronic arthritis. Acta Paediatr 84, 952-954 https://doi.org/10.1111/j.1651-2227.1995.tb13803.x
  10. Fakhoury M, Negrulj R, Mooranian A, Al-Salami H (2014) IBD: clinical aspects and treatments. J Inflamm Res 7, 113-120 https://doi.org/10.2147/jir.s65979
  11. Park E and Chung SW (2019) ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell Death Dis 10, 822 https://doi.org/10.1038/s41419-019-2064-5
  12. Kwon MY, Hwang N, Lee SJ and Chung SW (2019) NOD2 attenuates ER stress-induced cell death in VSMCs. BMB Rep 52, 665-670 https://doi.org/10.5483/bmbrep.2019.52.11.176
  13. Hwang N, Kwon MY, Woo JM and Chung SW (2019) Oxidative stress-induced pentraxin 3 expression human RPE cells is involved in the pathogenesis of AMD. Int J Mol Sci 20, 6028 https://doi.org/10.3390/ijms20236028