J Pharm Pharmacol. 2017 Aug 4. doi: 10.1111/jphp.12789. [Epub ahead of print]

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

da Silva LM1, Frión-Herrera Y1, Bartolomeu AR1, Gorgulho CM1, Sforcin JM1.

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Abstract

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.

© 2017 Royal Pharmaceutical Society.

PMID: 28776672 DOI: 10.1111/jphp.12789

 

* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.