TY - GEN
T1 - Photodynamic activity of porphines on tubulin assembly
AU - Ringel, Israel
AU - Gottfried, Varda
AU - Levdansky, Lila
AU - Winkelman, James W.
AU - Kimel, Sol
PY - 1996
Y1 - 1996
N2 - 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 (TPPS n) 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, TPPS 2o was found to be the most potent inhibitor, followed by TPPS 2a and to a much smaller extent by TPPS 4. All THPP isomers have negligible inhibitory effect. Upon exposure to white light, microtubule assembly was inhibited in the same order:TPPS 2o greater than TPPS 2a greater than TPPS 4 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.
AB - 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 (TPPS n) 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, TPPS 2o was found to be the most potent inhibitor, followed by TPPS 2a and to a much smaller extent by TPPS 4. All THPP isomers have negligible inhibitory effect. Upon exposure to white light, microtubule assembly was inhibited in the same order:TPPS 2o greater than TPPS 2a greater than TPPS 4 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.
UR - http://www.scopus.com/inward/record.url?scp=0029710227&partnerID=8YFLogxK
M3 - ???researchoutput.researchoutputtypes.contributiontobookanthology.conference???
AN - SCOPUS:0029710227
SN - 0819419893
SN - 9780819419897
T3 - Proceedings of SPIE - The International Society for Optical Engineering
SP - 156
EP - 163
BT - Proceedings of SPIE - The International Society for Optical Engineering
A2 - Ehrenberg, Benjamin
A2 - Jori, Giulio
A2 - Moan, Johan
T2 - Photochemotherapy: Photodynamic Therapy and Other Modalities
Y2 - 14 September 1995 through 16 September 1995
ER -
