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Proceedings Paper

Photodynamic activity of porphines on tubulin assembly
Author(s): Israel Ringel; Varda Gottfried; Lila Levdansky; James W. Winkelman M.D.; Sol Kimel
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Paper Abstract

Porphyrins and porphine analogs have been shown to induce cytotoxic effects on cells and tissues after exposure to light, an effect which is currently being studied as a new modality for treatment of cancer, termed photodynamic therapy (PDT). One of the important factors in PDT is the preferential uptake of sensitizers by rapidly proliferating tissues. Previous studies showed that cytoskeletal structures are affected by porphyrin-induced PDT. In the present study we investigate the inhibitory efficiency of porphines on tubulin assembly in vitro. We analyze the efficiency of several sulfonated porphine isomers: tetraphenylporphine n-sulfonate (TPPSn) where n equals 4, 2a and 2o (a and o refer to adjacent and opposite substitution, respectively) and the structural isomers of tetra(o-,m-, and p-hydroxyphenyl)porphine (o-,m- ,p-THPP), in order to find a possible structure-activity relationship. The efficiency of the sensitizers was assayed by their capacity to inhibit microtubule assembly. Binding to monomeric tubulin is essential for effective inhibition of assembly, with or without exposure to light. Without exposure to light, TPPS2o was found to be the most potent inhibitor, followed by TPPS2a and to a much smaller extent by TPPS4. All THPP isomers have negligible inhibitory effect. Upon exposure to white light, microtubule assembly was inhibited in the same order:TPPS2o greater than TPPS2a greater than TPPS4 greater than THPP. All porphines were found to have high affinity to the same site on tubulin even those who had almost no dark effect on tubulin assembly (THPP). Addition of the porphines to assembled microtubules did not lead to their depolymerization even after prolonged irradiation. Since it was previously suggested that porphines may share the same binding site on tubulin as bis-ANS, a known tubulin assembly inhibitor, we performed competition studies with this inhibitor and the porphines. It was shown that bis-ANS does not share the same site on tubulin as the porphines and therefore their effects are additive.

Paper Details

Date Published: 31 January 1996
PDF: 8 pages
Proc. SPIE 2625, Photochemotherapy: Photodynamic Therapy and Other Modalities, (31 January 1996);
Show Author Affiliations
Israel Ringel, Hebrew Univ. (Israel)
Varda Gottfried, Technion--Israel Institute of Technology (Israel)
Lila Levdansky, Hebrew Univ. (Israel)
James W. Winkelman M.D., Harvard Medical School (United States)
Sol Kimel, Technion--Israel Institute of Technology (Israel)

Published in SPIE Proceedings Vol. 2625:
Photochemotherapy: Photodynamic Therapy and Other Modalities
Benjamin Ehrenberg; Giulio Jori; Johan Moan, Editor(s)

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