Browsing by Author "Potter, Gerard A."
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Item Metadata only Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation.(Spandidos, 2009) Androutsopoulos, Vasilis; Mahale, S.; Arroo, R. R. J.; Potter, Gerard A.Item Metadata only Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism(BioMed Central, 2008) Androutsopoulos, Vasilis; Arroo, R. R. J.; Hall, J. F.; Surichan, Somchaiya; Potter, Gerard A.Item Metadata only Bioactivation of the phytoestrogen diosmetin by CYP1 cytochromes P450(Elsevier, 2009) Androutsopoulos, Vasilis; Wilsher, N.; Arroo, R. R. J.; Potter, Gerard A.Item Metadata only Cancer and related case studies involving salvestrol and CYP1B1(2012) Schaefer, B. A.; Potter, Gerard A.; Wood, R.; Burke, M. D.Item Metadata only The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1.(Nature Publishing Group, 2002-01-15) Potter, Gerard A.; Patterson, L. H.; Wanogho, E.; Perry, P. J.; Butler, P. C.; Ijaz, T.; Ruparelia, K. C.; Lamb, J. H.; Farmer, B.; Stanley, L. A.; Burke, M. D.Item Metadata only Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4'tetramethoxystilbene (DMU-212) on adenoma development in the Apc(Min+) mouse and cyclooxygenase-2 in human derived colon cancer cells.(Wiley, 2005-02-01) Potter, Gerard A.; Ruparelia, K. C.; Sale, S.; Tunstall, R. G.; Steward, William P.; Gescher, Andreas J.Item Open Access CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues(MDPI, 2024-01-15) Ruparelia, K. C.; Zeka, K.; Beresford, Kenneth J. M.; Wilsher, Nicola E.; Potter, Gerard A.; Androutsopoulos, V. P.; Brucoli, Federico; Arroo, R. R. J.Naturally occurring stilbenoids, such as the (E)-stilbenoid resveratrol and the (Z)-stilbenoid combretastatin A4, have been considered as promising lead compounds for the development of anticancer drugs. The antitumour properties of stilbenoids are known to be modulated by cytochrome P450 enzymes CYP1A1 and CYP1B1, which contribute to extrahepatic phase I xenobiotic and drug metabolism. Thirty-four methyl ether analogues of resveratrol were synthesised, and their anticancer properties were assessed, using the MTT cell proliferation assay on a panel of human breast cell lines. Breast tumour cell lines that express CYP1 were significantly more strongly affected by the resveratrol analogues than the cell lines that did not have CYP1 activity. Metabolism studies using isolated CYP1 enzymes provided further evidence that (E)-stilbenoids can be substrates for these enzymes. Structures of metabolic products were confirmed by comparison with synthetic standards and LC-MS co-elution studies. The most promising stilbenoid was (E)-4,3′,4′,5′-tetramethoxystilbene (DMU212). The compound itself showed low to moderate cytotoxicity, but upon CYP1-catalysed dealkylation, some highly cytotoxic metabolites were formed. Thus, DMU212 selectively affects proliferation of cells that express CYP1 enzymes.Item Metadata only Effects of the potential chemopreventive agent DMU-135 on adenoma development in the Apc(Min+) mouse.(Springer Verlag, 2006-02-24) Potter, Gerard A.; Butler, P. C.; Ruparelia, K. C.; Sale, S.; Tunstall, R. G.; Steward, William P.; Gescher, Andreas J.Item Metadata only Nutrition and cancer: Further case studies involving salvestrol.(Elsevier, 2010) Schaefer, B. A.; Dooner, C.; Burke, M. D.; Potter, Gerard A.Item Metadata only Pharmacokinetics in mice and growth inhibitory properties of the putative cancer chemopreventative agent resveratrol and the synthetic analogue trans-3,4,5,4'Tetramthoxystilbene.(Nature Publishing Group, 2004-02-01) Potter, Gerard A.; Boocock, D.; Sale, S.; Verschoyle, R. D.; Jones, D. J. L.; Wilsher, N.; Ruparelia, K. C.; Farmer, P. B.; Steward, William P.; Gescher, Andreas J.Item Metadata only Phytoestrogens as natural prodrugs in cancer prevention - a novel concept(Springer, 2008) Arroo, R. R. J.; Androutsopoulos, Vasilis; Patel, A.; Surichan, Somchaiya; Wilsher, N.; Potter, Gerard A.Item Metadata only Phytoestrogens as natural prodrugs in cancer prevention: Dietary flavonoids(Springer, 2009) Arroo, R. R. J.; Androutsopoulos, Vasilis; Beresford, Kenneth J. M.; Ruparelia, K. C.; Surichan, Somchaiya; Wilsher, N.; Potter, Gerard A.Item Open Access The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells(Elsevier, 2019-03-22) Lodhi, Sabahat; Ankrett, Dyan N.; Wilsher, Nicola E.; Potter, Gerard A.; Beresford, Kenneth J. M.; Arroo, R. R. J.; Ruparelia, K. C.As part of a programme to develop anticancer prodrugs which are activated by cytochrome P450 (CYP)1B1, a library of 4,6-diaryl-2-pyridones was synthesised in yields of 6-60% from the corresponding chalcones. A number of these derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing little toxicity towards a non-tumour breast cell line with no CYP expression. Metabolism studies provided evidence supporting the involvement of CYP1 enzymes in the bioactivation of these compounds.Item Open Access The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells(Bentham Science, 2017-12-11) Ruparelia, K. C.; Ljaza, T.; Ankrett, D. N.; Wilsher, Nicola Elizabeth; Lodhia, S.; Beresford, Kenneth J. M.; Bhambra, Avninder S.; Arroo, R. R. J.; Potter, Gerard A.; Butler, P. C.; Tan, Hoon Leong; Zeka, K.Abstract: Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objectives: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Results: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and -naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusions: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved.