Synergistic effects of photoactivated tetra(4-sulfonatophenyl)porphine and nocodazole on microtubule assembly, accumulation of cells in mitosis and cell survival.
Human carcinoma cells of the line NHIK 3025 were incubated with meso-tetra(4-sulfonatophenyl)porphine (TPPS4) for 18 h and exposed to light in the absence or presence of nocodazole. Nocodazole (1 microgram ml-1) was applied to the cells 15 min prior to light exposure and washed off the cells immediately afterwards. The presence of nocodazole during photoactivation of TPPS4-loaded cells leads to a significantly reduced ability of tubulin to repolymerize after withdrawal of nocodazole, an increased accumulation of the cells in mitosis with a larger fraction in c-metaphase and a higher yield of photoactivated cells. A higher proportion of the cells accumulating in mitosis 6-12 h after exposure to light is unable to form colonies when exposed to light in the presence of nocodazole than in its absence. The present results are consistent with a specific TPPS4-induced photodamage to the unpolymerized form of the microtubule components.
Berg
K
K
Institute for Cancer Research, Department of Biophysics, Montebello, Oslo, Norway.
Steen
H B
HB
Winkelman
J W
JW
Moan
J
J
D002278:Carcinoma in Situ; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008027:Light; D008870:Microtubules / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D008938:Mitosis; D008940:Mitotic Index / Q000187:drug effects / Q000528:radiation effects; D015739:Nocodazole / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms
D004273:DNA, Neoplasm; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D014404:Tubulin; C016136:tetraphenylporphine sulfonate; D015739:Nocodazole