A. Chelkowski Institute of Physics, Silesian Center for Education and Interdisciplinary Research, University of Silesia, Chorzow, Poland.
Institute of Chemistry, University of Silesia, Katowice, Poland.
J Photochem Photobiol B. 2019 Oct;199:111585. doi: 10.1016/j.jphotobiol.2019.111585. Epub 2019 Aug 8.
Thiosemicarbazone derivatives are known for their broad biological activity including their antitumor potency. The aim of the current study was to examine the effect of a novel series of non-toxic iron chelators on the accumulation of protoporphyrin IX after external 5-aminolevulonic acid administration. From this series we selected one the most promising derivative which causes a pronounced increase in the concentration of protoporphyrin IX. The increase of the photosensitizer concentration is necessary for the trigger the efficient therapeutic effect of the photodynamic reaction. For selected compound 2 we performed an examination of a panel of the genes that are involved in the heme biosynthesis and degradation. Results indicated the crucial roles of ferrochelatase and heme oxygenase in the described processes. Surprisingly, there was a strict dependence on the type of the tested cell line. A decrease in the expression of the two aforementioned enzymes after incubation with compound 2 and 5-aminolevulonic acid is a commonly known fact and we detected this trend for the MCF-7 and HCT 116 cell lines. However, we noticed the upregulation of the tested targets for the Hs683 cells. These unconventional results prompted us to do a more in-depth analysis of the described processes. In conclusion, we found that compound 2 is a novel, highly effective booster of photodynamic therapy that has prospective applications.
噻唑烷酮衍生物以其广泛的生物活性而闻名，包括其抗肿瘤活性。本研究的目的是研究一系列新型无毒铁螯合剂对 5-氨基酮戊酸给药后原卟啉 IX 积累的影响。在这个系列中，我们选择了一种最有前途的衍生物，它能显著增加原卟啉 IX 的浓度。增加光敏剂的浓度是触发光动力反应有效治疗效果所必需的。对于选定的化合物 2，我们对一组参与血红素生物合成和降解的基因进行了检查。结果表明，亚铁螯合酶和血红素加氧酶在所述过程中起着关键作用。令人惊讶的是，这与所测试的细胞系的类型有严格的依赖性。在用化合物 2 和 5-氨基酮戊酸孵育后，两种上述酶的表达下降是众所周知的事实，我们在 MCF-7 和 HCT 116 细胞系中检测到了这种趋势。然而，我们注意到 Hs683 细胞中测试靶标的上调。这些非传统的结果促使我们对所述过程进行更深入的分析。总之，我们发现化合物 2 是一种新型的、高效的光动力治疗增强剂，具有广阔的应用前景。
