Mechanisms involved in the cytotoxic action of Brazilian propolis and caffeic acid against HEp-2 cells and modulation of P-glycoprotein activity

Autor(es)

da Silva, Livia M. ^[1] ; Frion-Herrera, Yahima ^[1] ; Bartolomeu, Ariane R. ^[1] ; Gorgulho, Carolina Mendonca ^[1] ; Sforcin, Jose M. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Dept Microbiol & Immunol, Inst Biosci, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmacy and Pharmacology; v. 69, n. 11, p. 1625-1633, NOV 2017.
• Citações Web of Science: 7

Resumo

Objectives The effects of propolis and phenolic compounds (caffeic acid - Caf; dihydrocinnamic acid - Cin; p-coumaric acid - Cou) in the same quantity found in our propolis sample were investigated on human laryngeal epidermoid carcinoma (HEp-2) cells. Methods Cell viability, apoptosis/necrosis and cell cycle arrest, P53 and CASPASE-3 gene expression, generation of reactive oxygen species (ROS) and the ability of propolis to induce doxorubicin (DOX) efflux using a P-glycoprotein (P-gp) inhibitor (verapamil) were assayed. Key findings Propolis exerted a cytotoxic effect on HEp-2 cells, whereas isolated compounds had no effect on cell viability. Higher concentrations were tested and Caf induced late apoptosis or necrosis in HEp-2 cells, while propolis induced apoptosis, both probably due to ROS generation. P53 expression was downregulated by propolis but not by Caf. CASPASE-3 expression was correlated with induction of both early and late apoptosis, with both propolis and Caf alone upregulating its expression. Propolis induced cell cycle arrest at G2/M phase and Caf at S phase. Propolis but not Caf may act as a P-gp inhibitor by modulating P-gp activity and inhibiting DOX efflux. Conclusions Propolis exerted cytotoxic effects on HEp-2 cells, and the mechanisms are discussed, showing its potential as an antitumour drug. (AU)

• Processo FAPESP: 14/13245-4 - Possível ação sinérgica de componentes da própolis sobre células de carcinoma de laringe humana (HEp-2): mecanismos de resistência e morte celular
• Beneficiário: Lívia Matsumoto da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado