Abstract 4626: The mechanism and structure localization relationship studies of a small organic molecule as a fluorescent tumor marker

Abstract

Abstract BMVC, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide, is a novel organic molecule with special tumor recognition characteristic. BMVC appears bright fluorescence in the nucleus of cancer cells while only weak fluorescence in the cytoplasm of normal cells. The strong fluorescence of BMVC in the nucleus is mainly due to significant enhancement of BMVC fluorescence upon binding to DNA. Therefore, these distinct properties of BMVC in cells allow us to differentiate cancer cells from normal cells. It appears that BMVC is a potential fluorescent tumor marker. It is of interest to elucidate the reason why BMVC can act as a potential fluorescence tumor marker. Confocal microscopic images by merging with organelle trackers suggested that BMVC mainly localizes in the nucleus and mitochondria of cancer cells, but in the lysosome of normal cells. Several leading experiments suggested that the major pathway for BMVC uptake is endocytosis. In addition, the carbonyl-cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) and microinjection experiments showed that the destination of endocytosed BMVC is trapped in the lysosome of normal cells. However, it is not clear why BMVC is not trapped in the lysosome of cancer cells. Since the lysosomal membrane permeabilization (LMP) could sensitize cancer cell to death, we performed the cathepsin immunofluorescence and vacuolization experiments to elucidate whether there is LMP difference between cancer and normal cells. Our results showed that the LMP indeed plays an important role for trapping BMVC in the lysosome of normal cells, but releasing BMVC to the nucleus and mitochondria of cancer cells. Furthermore, the structure localization relationship (SLR) studies show that BMVC derivatives with large hydrogen bonding capacity (HBC) are less lysosomal membrane permeable in normal cells. In addition, we found the more lipophilic of BMVC derivatives the more mitochondria localization in cancer cells. It is likely that the HBC and the lipophilicity are two important characters in determining intracellular localization of BMVC derivatives in cells. In summary, the LMP and SLR studies of BMVC and its derivatives demonstrated a new direction for further design and synthesis of better fluorescent tumor markers and also provided a new platform for cancer selective drug through the combination of a cancer targeting molecule and anticancer drug. Reference: [1] C. C. Kang, C. C. Chang, T. C. Chang, L. J. Liao, P. J. Lou, W. Xie, E. S. Yeung, Analyst 2007, 132, 745. [2] L. J. Liao, C. C. Kang, I. S. Jan, H. C. Chen, C. L. Wang, P. J. Lou, T. C. Chang, Analyst 2009, 134, 708. [3] N. Fehrenbacher, M. Jaattela, Cancer Res 2005, 65, 2993. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4626.