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

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

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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 7 breast cancer cell lines, applying western blotting, gene expression analysis, fluorescence microscopy, and immunohistochemistry to 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 expression of genes controlling cell cycle and apoptosis . Fluorescence microscopy showed the compound’s mitochondrial targeting and ROS-modulating properties, inducing superoxide production at concentrations associated with anti-proliferative effects. A preliminary in vivo study in mice implanted with the MDA-MB-231 breast cancer xenograft showed that Oncamex inhibited tumour growth, reduced tissue viability and Ki-67 proliferation, with no overall systemic toxicity. Conclusion: 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
JournalBritish Journal of Cancer
Issue number8
Early online date31 Mar 2016
Publication statusPublished - 13 Apr 2016

    Research areas

  • Novel flavonoids, Preclinical models of cancer, ROS modulation, Breast cancer, Animal models of cancer, Natural products, SAR studies, Xenograft models, Novel antitumour agents

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