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

Author:

León Daniela1234,Reyes María Elena5,Weber Helga6,Gutiérrez Álvaro1237,Tapia Claudio128,Silva Ramón5,Viscarra Tamara1236,Buchegger Kurt234,Ili Carmen123ORCID,Brebi Priscilla123

Affiliation:

1. Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4780000, Chile

2. Millennium Institute of Immunology and Immunotherapy, Santiago 8320165, Chile

3. BMRC, Biomedical Reasearch Consortium-Chile, Santiago 8320165, Chile

4. Departamento de Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4780000, Chile

5. Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Temuco 4810101, Chile

6. Biomedicine and Traslational Research Laboratory, Centro de Excelencia en Medicina Traslacional (CEMT), Universidad de La Frontera, Temuco 4780000, Chile

7. Doctorado en Ciencias Mención Biología Celular y Molecular Aplicada, Universidad de La Frontera, Temuco 4780000, Chile

8. Carrera de Biotecnología, Facultad de Ciencias Agropecuarias y Medioambiente, Universidad de La Frontera, Temuco 4780000, Chile

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.

Funder

National Funding for Scientific and Technologic Development of Chile (FONDECYT) Postdoctorate project

Regular FONDECYT project

FONDEF Idea

Millennium Institute on Immunology and Immunotherapy

ANID scholarship

CORFO BMRC, Biomedical research consortium-Chile

Publisher

MDPI AG

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