In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2114-2114
Abstract:
The DNA repair protein BRCA2, initially discovered as a tumor suppressor for familial breast cancer cases, is now found to play critical role in the biology of many eukaryotes. The extracellular protozoan parasite Trypanosoma brucei significantly relies on its BRCA2 protein for stress management as well as surviving from host humoral immunity during its mammalian stage of its complex digenetic life cycle. An interesting aspect of BRCA2 deficiency in cancer cells is that these cells are ultra-sensitive to the inhibitors of the chromatin modifying enzyme poly(ADP-ribose) polymerase (PARP). In the absence of PARP, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Thus, PARP activity is essential in homologous recombination-deficient BRCA2-mutant cancer cells. BRCA2 and PARP are not only expressed in the mammalian cells but also present in high levels in many other eukaryotic cells including the parasitic protozoan T. brucei. To evaluate the universality of the importance of these two proteins in the management of DNA damage, we determined the effect of PARP inhibitors such as 3-AB, Veliparib, PF-01367338, Olaparib and Iniparib in BRCA2 knocked down T. brucei cells treated with the DNA damaging agent cisplatin. Our in vitro data strongly suggest that a combination of a BRCA2 inhibitor (e.g. BRCA2 BRC peptide), a PARP inhibitor and a DNA damaging agent (e.g. cisplatin) will be a chemical regimen for the management of trypanosomiasis and similar protozoan infections. Supported by NIH grants 2SC1GM081146-05 to MC, 1U54RR026140-01 to SM and NIH grants R01AI042327, R21AI076757 to GC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2114. doi:1538-7445.AM2012-2114
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-2114
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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