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KMID : 0624620200530050284
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BMB Reports
2020 Volume.53 No. 5 p.284 ~ p.289
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Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells
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Hwang Na-Rae
Chung Su-Wol
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Abstract
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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.
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KEYWORD
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Autophagic cell death, Pyroptosis, RPE, Sulfasalazine, Tamoxifen
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