Flavanoid Dimers from Brazilian Red Propolis have Anti-Proliferative Activity on Cancer Cells

A multi-institutional collaborative effort has recently resulted in the discovery of eight new flavonoid dimers from the Brazilian red propolis with anti-proliferative activity on cancer cells. These results have been published recently in the Journal of Natural Products.

This project started a few years ago when Professor Ronaldo A. Pilli (Instituto de Química – UNICAMP, Brazil) contacted me to develop a collaborative project involving Professor Severino Alencar’s PhD student Thais Banzato (both at ESALQ-USP).Working together with the teams of Dr. Debora Vendramini-Costa (Fox Chase Cancer Center, Philadelphia, PA, USA), Prof. Ronaldo Pilli and of Prof. João Ernesto de Carvalho (Faculdade de Ciências Farmacêuticas – UNICAMP), Thais and Prof. Severino discovered that red propolis extract displayed good antiproliferative activity on different cancer cells. Nevertheless, the red propolis extract presented a complex mixture of components that needed to be separated using bioassay-guided isolation.

Thais worked during several months at the Instituto de Química de São Carlos, together with Drs. Juliana R. Gubiani and Afif F. Monteiro (both as post-doctoral researchers at that time) and Darlon I. Bernardi (PhD student). The efforts of these four lab members was noteworthy, since the isolation of structurally closely related flavonoid dimers was challenging. Moreover, structure analysis showed a few structure variations that needed a very careful spectroscopic assignment. This was a true team effort, that ultimately led to the discovery of propolones A–D (1–4), propolonones A–C (5–7) and propolol A (8).

The antiproliferative activity of the major metabolites, propolone B (2) and propolonone A (5), was evaluated on glioma cells (U-251), breast cancer cells (MCF7), ovarian cancer cells expressing a multiple drug resistance phenotype (NCI-ADR/RES), and prostate (PC-3) cancer cells. Propolone B (2) and propolonone A (5) presented antiproliferative action on NCI-ADR/RES, indicating that 2 and 5 may overcome the multidrug resistance mechanism.

Read the complete results of this investigation in the Journal of Natural Products.