Gawecki Robert, Polanski Jaroslaw, Mrozek-Wilczkiewicz Anna
A. Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzow, Poland.
Institute of Chemistry, University of Silesia, 40-007 Katowice, Poland.
Int J Mol Sci. 2022 Dec 6;23(23):15370. doi: 10.3390/ijms232315370.
Photodynamic therapy is one of the most patient friendly and promising anticancer therapies. The active ingredient is irradiated protoporphyrin IX, which is produced in the body that transfers energy to the oxygen-triggering phototoxic reaction. This effect could be enhanced by using iron chelators, which inhibit the final step of heme biosynthesis, thereby increasing the protoporphyrin IX concentration. In the presented work, we studied thiosemicarbazone derivative, which is a universal enhancer of the phototoxic effect. We examined several genes that are involved in the transport of the heme substrates and heme itself. The results indicate that despite an elevated level of ABCG2, which is responsible for the PpIX efflux, its concentration in a cell is sufficient to trigger a photodynamic reaction. This effect was not observed for 5-ALA alone. The analyzed cell lines differed in the scale of the effect and a correlation with the PpIX accumulation was observed. Additionally, an increased activation of the iron transporter MFNR1 was also detected, which indicated that the regulation of iron transport is essential in PDT.
光动力疗法是最受患者欢迎且最具前景的抗癌疗法之一。其活性成分是经照射的原卟啉IX，它在体内产生并将能量传递给氧引发光毒性反应。使用铁螯合剂可增强这种效应，铁螯合剂能抑制血红素生物合成的最后一步，从而提高原卟啉IX的浓度。在本研究中，我们研究了硫代氨基脲衍生物，它是光毒性效应的通用增强剂。我们检测了几个参与血红素底物和血红素自身转运的基因。结果表明，尽管负责原卟啉IX外排的ABCG2水平升高，但其在细胞中的浓度足以引发光动力反应。单独使用5-氨基乙酰丙酸未观察到这种效应。分析的细胞系在效应程度上存在差异，且观察到与原卟啉IX积累存在相关性。此外，还检测到铁转运蛋白MFNR1的激活增加，这表明铁转运的调节在光动力疗法中至关重要。
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