Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models

Carlos Martínez-Pérez, Carol Ward, Arran K Turnbull, Peter Mullen, Graeme Cook, James Meehan, Edward J Jarman, Patrick I T Thomson, Colin J Campbell, Donald McPhail, David J Harrison, Simon P Langdon

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Abstract

BACKGROUND: The natural polyphenol myricetin induces cell cycle arrest and apoptosis in preclinical cancer models. We hypothesised that myricetin-derived flavonoids with enhanced redox properties, improved cell uptake and mitochondrial targeting might have increased potential as antitumour agents.

METHODS: We studied the effect of a second-generation flavonoid analogue Oncamex in a panel of seven breast cancer cell lines, applying western blotting, gene expression analysis, fluorescence microscopy and immunohistochemistry of xenograft tissue to investigate its mechanism of action.

RESULTS: Proliferation assays showed that Oncamex treatment for 8 h reduced cell viability and induced cytotoxicity and apoptosis, concomitant with increased caspase activation. Microarray analysis showed that Oncamex was associated with changes in the expression of genes controlling cell cycle and apoptosis. Fluorescence microscopy showed the compound's mitochondrial targeting and reactive oxygen species-modulating properties, inducing superoxide production at concentrations associated with antiproliferative effects. A preliminary in vivo study in mice implanted with the MDA-MB-231 breast cancer xenograft showed that Oncamex inhibited tumour growth, reducing tissue viability and Ki-67 proliferation, with no signs of untoward effects on the animals.

CONCLUSIONS: Oncamex is a novel flavonoid capable of specific mitochondrial delivery and redox modulation. It has shown antitumour activity in preclinical models of breast cancer, supporting the potential of this prototypic candidate for its continued development as an anticancer agent.

Original languageEnglish
Pages (from-to)905-916
Number of pages12
JournalBritish Journal of Cancer
Volume114
Issue number8
DOIs
Publication statusPublished - 31 Mar 2016
Externally publishedYes

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Keywords

  • cell survival
  • antineoplastic agents
  • flavonoids
  • breast neoplasms

Cite this

Martínez-Pérez, C., Ward, C., Turnbull, A. K., Mullen, P., Cook, G., Meehan, J., ... Langdon, S. P. (2016). Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models. British Journal of Cancer, 114(8), 905-916. https://doi.org/10.1038/bjc.2016.6