Differential in radiosensitizing potency of enantiomers of the fatty acid synthase inhibitor C75

Rae, C. , Babich, J. W. and Mairs, R. J. (2017) Differential in radiosensitizing potency of enantiomers of the fatty acid synthase inhibitor C75. Chirality, 29(1), pp. 10-13. (doi: 10.1002/chir.22668) (PMID:27901292) (PMCID:PMC5248592)

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The elevated activity of fatty acid synthase has been reported in a number of cancer types. Inhibition of this enzyme has been demonstrated to induce cancer cell death and reduce tumor growth. In addition, the fatty acid synthase inhibitor drug C75 has been reported to synergistically enhance the cancer-killing ability of ionizing radiation. However, clinical use of C75 has been limited due to its producing weight loss, believed to be caused by alterations in the activity of carnitine palmitoyltransferase-1. C75 is administered in the form of a racemic mixture of (−) and (+) enantiomers that may differ in their regulation of fatty acid synthase and carnitine palmitoyltransferase-1. Therefore, we assessed the relative cancer-killing potency of different enantiomeric forms of C75 in prostate cancer cells. These results suggest that (−)-C75 is the more cytotoxic enantiomer and has greater radiosensitizing capacity than (+)-C75. These observations will stimulate the development of fatty acid synthase inhibitors that are selective for cancer cells and enhance the tumor-killing activity of ionizing radiation, while minimizing weight loss in cancer patients.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Mairs, Professor Robert and Rae, Dr Colin
Authors: Rae, C., Babich, J. W., and Mairs, R. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Chirality
ISSN (Online):1520-636X
Published Online:30 November 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Chirality 29(1): 10-13
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
609641Enhancement of prostate targeted radiotherapy using PSMA-seeking agents in combination with radiosensitizers.Robert MairsThe Prostate Cancer Charity (PROST-CHAR)PG12-12ICS - EPIGENETICS