Abstract A128: Dual properties of fluorescence probe and anticancer agent of small molecules developed for cancer research

• Published in: Molecular cancer therapeutics 2011-11, Vol.10 (11_Supplement), p.A128-A128
• Main Authors: Chang, TaChau, Huang, Wei-Chun, Wang, Zi-Fu, Cho, Chih-Chien
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-11-A128

The dual properties of fluorescence probe for cancer diagnosis and G-quadruplex (G4) stabilizer for cancer treatment of 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) [1,2] inspire us to develop second-generation BMVC derivatives. A number of distinct BMVC derivatives were synthesized to investigate the correlation between cellular response and biological function of BMVC derivatives for cancer treatment. The fluorescence properties of BMVC derivatives allow us to visualize the cellular localization and possibly monitor the drug-target interaction. Together with their biological and toxicological analyzes, the correlation between cellular response and biological function of BMVC derivatives may allow us to elucidate their therapeutic mechanisms for cancer treatments. Here we have evaluated the efficacy of two BMVC derivatives, 3,6-bis(1-methyl-4-vinylpyridinium iodide)-9-(1-(1-methyl-piperidinium iodide)-3,6,9-trioxaundecane) carbazole (BMVC-8C3O) and 3,6-bis(1-methyl-4-vinylpyridinium iodide)-9-(1-(1-methyl-piperidinium iodide) dodecyl) carbazole (BMVC-12C), in CL1-0 cancer treatment. Both molecules are mainly detected in lysosome of MRC-5 normal cells. However, BMVC-12C is mainly accumulated in mitochondria of cancer cells, while BMVC-8C3O is distributed in nucleus and mitochondria of cancer cells. Although BMVC-8C3O is a better G4 stabilizer than BMVC-12C to human telomeres, BMVC-12C inhibits population doubling of CL1-0 cancer cells earlier than BMVC-8C3O. Apparently, they have different therapeutic mechanisms. Fluorescence imaging showed competition of BMVC-12C with Mitotracker red into mitochondria, implying that BMVC-12C probably accumulates into mitochondria inner membrane. The accumulation of BMVC-12C in mitochondria induces cytochrome C release and cell death. In addition, CL1-0 cancer cells treated by BMVC-12C for 72 h will lose mitochondria membrane potential and increase the level of reactive oxygen species. Our results suggest that BMVC-12C is a novel mitochondriotoxic molecule. References: 1. L.J. Liao, et al. Analyst 134, 708 (2009). 2. F.Z. Huang, et al. Mol. Cancer Res. 6, 955 (2008). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A128.