Antitumour activity of the novel flavonoid oncamex in preclinical breast cancer models
MetadataShow full item record
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.
Martínez-Pérez , C , Ward , C , Turnbull , A K , Mullen , P , Cook , G , Meehan , J , Jarman , E J , Thomson , P I T , Campbell , C J , McPhail , D , Harrison , D J & Langdon , S P 2016 , ' Antitumour activity of the novel flavonoid oncamex in preclinical breast cancer models ' British Journal of Cancer , vol. 114 , no. 8 , pp. 905-916 . DOI: 10.1038/bjc.2016.6
British Journal of Cancer
This work is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
DescriptionWe thank SULSA (Scottish Universities Life Science Alliance) for supporting this project through a SULSA BioSkape Industry PhD Studentship and Antoxis Limited for providing additional funding. We also thank the 7th Framework Programme of the European Union (METOXIA project; HEALTH-F2-2009-222741) for support.
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Showing items related by title, author, creator and subject.
Determinants of fertility issues experienced by young women diagnosed with breast or gynaecological cancer - a quantitative, cross-cultural study Sobota, Aleksandra; Ozakinci, Gozde (2018-09-06) - Journal articleBackground. Although there is a recognition of the importance of fertility to young women with cancer, we do not know who is at risk of distress related to fertility issues following diagnosis. We investigated the determinants ...
A systematic review of the supportive care needs of people living with and beyond cancer of the colon and/or rectum Kotronoulas, Grigorios; Papadopoulou, Constantina; Cunningham, Kathryn; Simpson, Mhairi; Maguire, Roma (2017-08) - Journal itemPurpose: Gaining a clear understanding of the health needs and concerns of people with cancer of the colon and/or rectum can help identify ways to offer a comprehensive care package. Our aim was to systematically assess ...
Customizing the therapeutic response of signaling networks to promote antitumor responses by drug combinations Goltsov, A.; Langdon, S.P.; Goltsov, G.; Harrison, D.J.; Bown, J. (2014-02-05) - Journal articleDrug resistance, de novo and acquired, pervades cellular signaling networks (SNs) from one signaling motif to another as a result of cancer progression and/or drug intervention. This resistance is one of the key determinants ...