In Vitro Effect of Epigallocatechin Gallate on Heme Synthesis Pathway and Protoporphyrin IX Production

IF 5.5 3区材料科学 Q2 CHEMISTRY, PHYSICAL ACS Applied Energy Materials Pub Date : 2024-08-09 DOI:10.3390/ijms25168683

Daniela León, M. E. Reyes, Helga Weber, Álvaro Gutiérrez, Claudio Tapia, Ramón Silva, T. Viscarra, K. Buchegger, C. Ili, P. Brebi

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Abstract

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG’s role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells.

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表没食子儿茶素没食子酸酯对血红素合成途径和原卟啉 IX 生成的体外影响

光动力疗法（PDT）可治疗非黑色素瘤皮肤癌。光动力疗法通过细胞中的氧气、光敏剂和特定光线相互作用产生的活性氧（ROS）杀死细胞。原卟啉 IX（PpIX）是一种光敏剂，由氨基乙酰丙酸甲酯（MAL）通过血红素组合成（HGS）途径产生。在抗 PDT 细胞中，加入表没食子儿茶素没食子酸酯（EGCG）可提高 PDT 的疗效。因此，本研究旨在评估 EGCG 的特性对 A-431 细胞系 MAL-TFD 和 PpIX 生成的影响。评估了 EGCG 对 A-431 细胞株细胞增殖（流式细胞仪和伤口愈合检测）和克隆生成能力（克隆生成检测）的作用，并通过细胞活力检测（MTT）、PpIX 和 ROS 检测（流式细胞仪）、细胞内铁定量和 HGS 酶的基因表达（RT-qPCR）确定了 EGCG 对 MAL-PDT 的影响。低浓度的EGCG（<50 µM）对A-431细胞没有抗增殖作用；但是，EGCG抑制了细胞的克隆能力。此外，EGCG（<50 µM）还能提高 MAL-PDT 的细胞毒性，增加 PpIX 和 ROS 水平，对 PpIX 合成产生积极影响，降低细胞内铁浓度，改变 HGS 酶基因的表达，如 PGB（上调）和 FECH（下调）。EGCG 可抑制克隆生成能力并调节 PpIX 的合成，从而提高 PDT 对耐药细胞的疗效。

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来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.