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Differential Uptake and Selective Permeability of Fusarochromanone (FC101), a Novel Membrane Permeable Anticancer Naturally Fluorescent Compound in Tumor and Normal Cells

Published online by Cambridge University Press:  16 September 2009

Brian D. Furmanski ,
Didier Dréau ,
Roy E. Wuthier  and
John W. Fuseler
Brian D. Furmanski
Affiliation:
Department of Chemistry and Biochemistry, University of South Carolina, 337 Graduate Science Research Center, Columbia, SC 29208
Didier Dréau
Affiliation:
Department of Biology, University of North Carolina-Charlotte, 9201 University City Blvd., Charlotte, NC 28223
Roy E. Wuthier
Affiliation:
Department of Chemistry and Biochemistry, University of South Carolina, 337 Graduate Science Research Center, Columbia, SC 29208
John W. Fuseler*
Affiliation:
Department of Cell Biology and Anatomy, University of South Carolina, School of Medicine Campus 661, B-58, Columbia, SC 29209
*
Corresponding author. E-mail: [email protected]
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Abstract

The differential accumulation of fluorescent molecules in tumorigenic versus normal cells is a well-reported phenomenon and is the basis for photodiagnostic therapy. Through the use of confocal microscopy, the kinetic uptake and accumulation of fusarochromanone (FC101) was determined in two lines of living tumorigenic cells of mesenchymal-epithelial origin and normal fibroblast cells. Like other fluorescent cationic molecules, FC101 showed increased accumulation in tumorigenic cells; however, unlike other molecules, it appeared to be accumulated in a time-dependent manner. Also, unlike traditional fluorescent cationic molecules, FC101, a potent inhibitor of cell growth, showed preferential inhibition of tumorigenic B-16 melanoma cells and MCF7 cells derived from breast cancer adenocarcinoma when compared to normal cardiac fibroblasts. Further analysis of FC101's physicochemical properties using both experimentally obtained and simulated values revealed the likelihood of membrane permeation and oral bioavailability of the compound. These physicochemical properties of FC101 were also used to predict its intracellular localization lending credence to data observed by confocal microscopy.

Keywords

fusarochromanone (FC101)confocal microscopyimage analysistransformed cellsnormal cellsdrug uptake
Type
Biological Science Applications
Information
Microscopy and Microanalysis , Volume 15 , Issue 6 , December 2009 , pp. 545 - 557
Copyright
Copyright © Microscopy Society of America 2009

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References

REFERENCES

ACD (2007). ACD/PhysChem Predictor, version 11.00. Toronto, ON, Canada: Advanced Chemistry Development, Inc. Available at http://www.acdlabs.com.Google Scholar
Allen, N.K., Jevne, R.L., Mirocha, C.J. & Lee, Y.W. (1982). The effect of a Fusarium roseum culture and diacetoxyscirpenol on reproduction of white leghorn females. Poul Sci 61, 2172–2175.CrossRefGoogle ScholarPubMed
Altenburg, G.A., Vanoye, C.G., Horton, J.K. & Reuss, L. (1994). Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells: Evidence against direct drug extrusion from the plasma membrane. Proc Natl Acad Sci 91, 4654–4657.CrossRefGoogle Scholar
Bulychev, A. & Trouet, A. (1978). Uptake and intracellular distribution of neutral red in cultured fibroblasts. Exp Cell Res 115, 343–355.CrossRefGoogle ScholarPubMed
Dreau, D., Foster, M., Hogg, M., Culberson, C., Nunes, P. & Wuthier, R.E. (2007). Inhibitory effects of fusarochromanone on melanoma growth. Anti-Cancer Drugs 18, 897–904.CrossRefGoogle ScholarPubMed
Eytan, G.D., Regev, R., Oren, G. & Assaraf, Y.G. (1996). The role of passive transbilayer drug movement in multidrug resistance and its modulation. J Biol Chem 271, 12897–12902.CrossRefGoogle ScholarPubMed
Fuseler, J.W., Merrill, D.W., Grisham, M.B. & Wolf, R.E. (2006). Analysis and quantitation of NF-kB nuclear translocation in tumor necrosis factor alpha activated vascular endothelial cells. Microsc Microanal 12, 269–276.CrossRefGoogle ScholarPubMed
Fuseler, J.W., Millette, C.F., Davis, J.M. & Carver, W. (2007). Fractal and image analysis of morphological changes in the actin cytoskeleton of neonatal cardiac fibroblasts in response to mechanical stretch. Microsc Microanal 13, 128–132.CrossRefGoogle ScholarPubMed
Horobin, R.W., Stockert, J.C. & Rashid-Doubell, F. (2006). Fluorescent cationic probes for nuclei of living cells: Why are they selective? A quantitative structure-activity relations analysis. Histochem Cell Biol 126, 165–175.CrossRefGoogle ScholarPubMed
Kramer, S.D. (1999). Absorption prediction from physicochemical parameters. Pharma Sci & Tech Today 2, 373–380.CrossRefGoogle ScholarPubMed
Lee, Y.-W., Mirocha, C.J., Shroeder, D. & Walser, M. (1985). TDP-1, a toxic component causing tibial dyschondroplasia in broiler chickens, and trichothecenes from Fusarium roseum, Graminerarum. Appl Environ Microbiol 50, 102–107.CrossRefGoogle Scholar
Lipinski, C.A., Lombardo, F., Dominy, B.W. & Feeney, P.J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 46, 3–26.CrossRefGoogle ScholarPubMed
Mayer, L.D., Bally, M.B. & Cullis, P.R. (1986). Uptake of adiamycin into large unilamellar vesicles in response to a pH gradient. Biochimica et Biophysica Acta 857, 123–126.CrossRefGoogle ScholarPubMed
Minervini, F., Lucivero, G., Visconti, A. & Bottalico, C. (1992). Immunomodulatory effects of fusarochromanones TDP-1 and TDP-2. Natural Toxins 1, 15–18.CrossRefGoogle ScholarPubMed
Nie, D. (1997). Effects of fusarochromanone on endothelial cells: Implications in deficient vascularization in the pathogenesis of avian tibial dyschondroplasia. PhD Thesis, University of South Carolina, Columbia, South Carolina.Google Scholar
OECD (1987). OECD Guideline for Testing of Chemicals. Paris, France: Organisation for Economic Co-operation and Development.Google Scholar
Rashid-Doubell, F. & Horobin, R.W. (1993). Selection of fluorescent golgi complex probes using structure-activity relationship models. In Biotechnology Applications of Microinjection, Microscopic Imaging, and Fluorescence, Bach, P.H. (Ed.), pp. 73–78. New York: Plenum Press.CrossRefGoogle Scholar
Rogers, J.A. & Fuseler, J.W. (2007). Regulation of NF-kB activation and nuclear translocation by exogenous nitric oxide (NO) donors in the TNF-a activated vascular endothelial cells. Nitric Oxide 16, 379–391.CrossRefGoogle Scholar
Sato, T., Hashizume, M., Hotta, Y. & Okahata, Y. (1998). Morphology and proliferation of B16 melanoma cells in the presence of lanthanoid and Al3+ ions. BioMetals 11, 107–112.CrossRefGoogle ScholarPubMed
Simon, S., Roy, D. & Schindler, M. (1994). Intracellular pH and the control of multidrug resistance. Proc Natl Acad Sci 91, 1128–1132.CrossRefGoogle ScholarPubMed
Spoelstra, E.C., Westerhoff, H.V., Dekker, H. & Lankelma, J. (1992). Kinetics of daunorubicin transport by P-glycoprotein of intact cancer cells. Eur J Biochem 207, 567–579.CrossRefGoogle ScholarPubMed
Vattulainen, I. (2005). Molecules dancing in membranes. Diffusion-Fundamentals 2, 113.1–113.15.Google Scholar
Veber, D.F., Johnson, S.R., Cheng, H.-Y., Smith, B.R., Ward, K.W. & Kopple, K.D. (2002). Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45, 2615–2623.CrossRefGoogle ScholarPubMed
Walser, M.M., Allen, N.K., Mirocha, C.J., Hanlon, G.F. & Newman, J.A. (1982). Fusarium-induced osteochondrosis (tibial dyschondroplasia) in chickens. Vet Pathol 19, 544–550.CrossRefGoogle ScholarPubMed
Walter, J.R.J. & Berns, M.W. (1986). Digital image processing and analysis. In Video Microscopy, pp. 327–392. New York, London: Plenum Press.CrossRefGoogle Scholar
Warburg, O. (1956). On the origin of cancer cells. Science 123, 309–314.CrossRefGoogle ScholarPubMed
Xie, W.P., Mirocha, C.J., Pawlosky, R.J., Wen, Y.C. & Xu, X.G. (1989). Biosynthesis of fusarochromanone and its monoacetyl derivative by Fusarium equiseti. Appl Environ Microbiol 55, 794–797.CrossRefGoogle ScholarPubMed
Yang, W.C. & Stasser, F.F. (1965). Mechanism of drug-induced vacuolization in tissue culture. Exp Cell Res 38, 495–506.CrossRefGoogle ScholarPubMed