Abstract 2604: PENAO: A novel tumor metabolism inhibitor for glioblastoma
2011; American Association for Cancer Research; Volume: 71; Issue: 8_Supplement Linguagem: Inglês
10.1158/1538-7445.am2011-2604
ISSN1538-7445
AutoresSylvia A. Chung, Pierre J. Dilda, Emma E. Ramsay, Charlie Teo, Philip J. Hogg, Kerrie L. McDonald,
Tópico(s)Cancer, Hypoxia, and Metabolism
ResumoAbstract Despite undeniable progress in the care and the treatment of primary brain tumors, for most patients diagnosed with glioblastoma (GBM) there is no realistic possibility of cure or even long term survival. Inherent resistance to conventional chemotherapy and irradiation are characteristic of GBM. Testing of new potential anti-tumorigenic drugs is needed. PENAO, (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is a mitochondrial toxin that inactivates inner-membrane adenine nucleotide translocase (ANT) resulting in proliferation arrest and apoptosis of tumor and tumor-supporting cells. The cytostatic efficacy of PENAO was tested on a panel of five commercial and primary GBM cell lines that differed in tumorigenicity, drug resistance, invasion and DNA repair. PENAO demonstrated an impressive anti-proliferative activity compared to carboplatin and temozolomide, drugs commonly used to treat GBM patients. The half maximal inhibitory concentration (IC50) values for PENAO were all in the low micromolar range. The increase in anti-proliferative activity for PENAO compared to carboplatin ranged from 6 to 200-fold. PENAO is a substrate for the multidrug resistant associated proteins 1 and 2 and inhibition of this transporter enhanced PENAO anti-proliferative activity from 2 to 8-fold. In conclusion, PENAO is a potent inhibitor of GBM cell line proliferation. This activity was superior to that observed with standard chemotherapeutics and warrants further in vivo investigations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2604. doi:10.1158/1538-7445.AM2011-2604
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