Photochemically generated elemental selenium forms conjugates with serum proteins that are preferentially cytotoxic to leukemia and selected solid tumor cells. Photochem Photobiol 2012;88(2):448-60
Date
01/04/2012Pubmed ID
22211823Pubmed Central ID
PMC3292634DOI
10.1111/j.1751-1097.2012.01078.xScopus ID
2-s2.0-84857995774 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
The objective of this study was to determine if and how photoproducts contribute to the antitumor effect of merocyanine-mediated PDT. A panel of barbituric, thiobarbituric and selenobarbituric acid analogues of Merocyanine 540 was photobleached, and the resulting photoproducts were characterized by absorption, fluorescence emission, mass, energy dispersive X-ray, and X-ray photoelectron spectroscopy and tested for cytotoxic activity against tumor cell lines and freshly explanted bone marrow cells. While all dyes were readily photobleached, only photoproducts of selone dyes showed cytotoxic activity. One-hour incubations with micromolar concentrations of selone-derived photoproducts were sufficient to reduce leukemia/lymphoma cells ≥10 000 fold, whereas preserving virtually all normal CD34-positive bone marrow cells. Of six multidrug-resistant tumor cell lines tested, five were as sensitive or more sensitive to photoproducts than the corresponding wild-type lines. Physicochemical characterizations of the cytotoxic activity indicated that it consisted of conjugates of subnano particles of elemental selenium and (lipo)proteins. The discovery of cytotoxic Se-protein conjugates provides a rare example of photoproducts contributing substantially to the antitumor effect of PDT and challenges the long-held view that Se in oxidation state zero is biologically inert. Agents modeled after our Se-protein conjugates may prove useful for the treatment of leukemia.
Author List
Daziano JP, Günther WH, Krieg M, Tsujino I, Miyagi K, Anderson GS, Sampson RW, Ostrowski MD, Muir SA, Bula RJ, Sieber FAuthor
Fritz Sieber PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BarbituratesBone Marrow Cells
Cell Line, Tumor
Cell Survival
Drug Resistance, Neoplasm
Humans
Light
Lipoproteins
Neoplasms
Photochemical Processes
Photochemotherapy
Photoelectron Spectroscopy
Photosensitizing Agents
Protein Binding
Pyrimidinones
Selenium Compounds
