Antitumoural activity of Brazilian red propolis fraction enriched with xanthochymol and formononetin: An in vitro and in vivo study Estela Maria Novak a,b,c, *, Martha Silveira e Costa Silva a , Maria Cristina Marcucci d , Alexandra Christine Helena Frankland Sawaya e , Begoña Giménez-Cassina López e , Maria Angela Henriques Zanella Fortes f , Ricardo Rodrigues Giorgi f , Kamila Tamie Marumo g , Rosangela Felipe Rodrigues h , Durvanei Augusto Maria h a Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP, Brazil b Laboratório de Investigação Médica(LIM-36)-ICR/HCFMUSP, São Paulo, SP, Brazil c Instituto de Tratamento do Câncer (ITACI)-ICR/HCFMUSP, São Paulo, SP, Brazil d Graduate Program in Biotechnology and Pharmacy University Bandeirante Anhanguera of São Paulo, SP, Brazil e Bioscience and Technology of Bioactive Products Postgraduate Program, Department of Plant Biology, Institute of Biology, State University of Campinas (UNICAMP), Brazil f Cellular and Molecular Endocrinology Laboratory, LIM-25. Faculty of Medicine, University of São Paulo, SP, Brazil g Lab Biochemistry and Biophysics, Butantan Institute, São Paulo, Brazil h Department of Surgery, Faculty of Veterinary Medicine and Animal Science of the University of São Paulo, SP, Brazil ARTICLE INFO Article history: Received 23 January 2014 Received in revised form 29 August 2014 Accepted 10 September 2014 Available online ABSTRACT In this study, ultra-high performance liquid chromatography-mass spectrometry and tandem mass spectrometry of selected ions were used to characterise the ethanolic extract of a sample of Brazilian red propolis (EEBRP) and an active fraction (BRP-IV) containing xanthochymol and formononetin. The antiproliferative effect of BRP-IV was assayed using melanoma tumour xenografts in mice and HL-60, K562, RPMI8226, B16F10 cell lines. This fraction inhibited growth of tumour cell lines with IC50 values of 20.5 ± 2.4 to 32.6 ± 2.6 µg/mL while EEBRP induced cytotoxic effect with IC50 values of 29.7 ± 1.5 to 42.1 ± 8.7 µg/mL. BRP-IV also inhibited the proliferation of B16F10 cells by blocking cell cycle progression in the G2/M phase and in- ducing apoptosis. Administration of 10 mg/kg/day BRP-IV suppressed the growth of B16F0 tumour xenografts in C57BL/6 mice with less general toxicity than control groups. Taken together, these results indicate that BRP-IV can be considered a promising anticancer drug for the treatment of human cancers. © 2014 Elsevier Ltd. All rights reserved. Keywords: Brazilian red propolis BRP-IV fraction Xanthochymol Formononetin Murine melanoma model Haematological cancer * Corresponding author. Fundação Pró-Sangue Hemocentro de São Paulo.Av. Dr. Eneas Carvalho de Aguiar, 155 - 1° andar, São Paulo, SP 05403-000, Brazil. Tel.: +55 1126618828; fax: +55 1126618782. E-mail address: enovak@usp.br (E.M. Novak). http://dx.doi.org/10.1016/j.jff.2014.09.008 1756-4646/© 2014 Elsevier Ltd. All rights reserved. journal of functional foods 11 (2014) 91–102 Available at www.sciencedirect.com ScienceDirect journal homepage: www.elsevier.com/locate/jff