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

Autor(es)

Lopes, Tairine Zara ^[1] ; de Moraes, Fabio Rogerio ^{[2, 3]} ; Tedesco, Antonio Claudio ^[4] ; Arni, Raghuvir Krishnaswamy ^{[2, 3]} ; Rahal, Paula ^[1] ; Calmon, Marilia Freitas ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Lab Genom Studies, Sao Jose Do Rio Preto, SP - Brazil

^[2] Sao Paulo State Univ, Phys Dept, Sao Jose Do Rio Preto, SP - Brazil

^[3] Sao Paulo State Univ, Multiuser Ctr Biomol Innovat, Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Ctr Nanotechnol & Tissue Engn Photobiol & Photome, Dept Chem, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 123, MAR 2020.
• Citações Web of Science: 5

Resumo

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. (AU)

• Processo FAPESP: 09/53989-4 - EMU: aquisição de espectrômetro de ressonância magnética nuclear para estudos de biomoléculas
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários