Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells

Tairine Zara Lopes; Fabio Rogério de Moraes; Antonio Claudio Tedesco; Raghuvir Krishnaswamy Arni; Paula Rahal; Marilia Freitas Calmon

Biomedicine & Pharmacotherapy (Mar 2020)

Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells

Tairine Zara Lopes,
Fabio Rogério de Moraes,
Antonio Claudio Tedesco,
Raghuvir Krishnaswamy Arni,
Paula Rahal,
Marilia Freitas Calmon

Affiliations

Tairine Zara Lopes: Laboratory of Genomics Studies, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
Fabio Rogério de Moraes: Physics Department, São Paulo State University, São José do Rio Preto, São Paulo, Brazil; Multiuser Center for Biomolecular Innovation, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
Antonio Claudio Tedesco: Department of Chemistry, Center of Nanotechnology and Tissue Engineering-Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, Brazil
Raghuvir Krishnaswamy Arni: Physics Department, São Paulo State University, São José do Rio Preto, São Paulo, Brazil; Multiuser Center for Biomolecular Innovation, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
Paula Rahal: Laboratory of Genomics Studies, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
Marilia Freitas Calmon: Laboratory of Genomics Studies, São Paulo State University, São José do Rio Preto, São Paulo, Brazil; Corresponding author at: Department of Biology, Instituto de Biociências, Letras e Ciências Exatas – IBILCE/UNESP, Cristóvão Colombo, 2265, 15054-000 São José do Rio Preto, SP, Brazil.

Journal volume & issue: Vol. 123
p. 109794

Abstract

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Renal cell carcinoma (RCC) consists of the most lethal common urological cancer and the clinical practice has shown that resistant RCC to commons therapies is extremely high. Berberine is an isoquinoline alkaloid, presents in different kinds of plants and it has long been used in Chinese medicine. It has several properties, such as antioxidant, anti-inflammatory, anti-diabetic, anti-microbial and anti-cancer. Moreover, berberine has photosensitive characteristics and its association with photodynamic therapy (PDT) is effective against tumor cells. This study aimed to evaluate the effects of berberine associated with PDT in renal carcinoma cell lines. The cellular viability assay showed increased cytotoxicity in concentration and time-dependent manner. Berberine presented efficient internalization in all cell lines analyzed. In addition, after treatment with berberine associated with PDT, it was observed a high phototoxicity effect with less than 20 % of viable cells. In this study we observed that the increase of reactive oxygen species (ROS) levels was accompanied by an increase of autophagy levels and apoptosis by caspase 3 activity, suggesting cell death by both mechanisms. Additionally, three target genes of anti-cancer drugs were differentially expressed in 786-O cells, being that Vascular Endothelial Growth Factor-D (FIGF) and Human Telomerase Reverse Transcriptase (TERT) gene presented low expression and Polo Like Kinase 3 (PLK3) presented overexpression after treatment with berberine associated with PDT. In this study, the proposed treatment triggered metabolites changes related to cell proliferation, tumorigenesis and angiogenesis. Thus, it was possible to suggest that berberine has promising potential as a photosensitizing agent in a photodynamic therapy, because it induced significant anticancer effects on renal carcinoma cells.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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