Tumor cell specific dark cytotoxicity of light-exposed merocyanine 540: implications for systemic therapy without light.
Merocyanine 540 (MC540) was activated by exposure to 514 nm laser light. The light-exposed MC540 was then mixed (in the dark) with tumor cells and normal cells to determine the antiproliferative activity. Treatment with light-exposed MC540 resulted in 70-90% tumor cell kill from different cell lines, while 85% of the normal human mononuclear cells and 41% of the granulocyte-macrophage colony forming cells (CFU-GM) survived the treatment. The observed cytotoxicity of light-exposed MC540 to the tumor cells was significantly greater (P less than 0.05) than the native MC540. Results show that tumor cell specificity and cytotoxicity in the light activated dye are retained for at least 30 days. Addition of catalase and mannitol decreased the cell kill by light-exposed compound, indicating that the observed effects may be due to reactive oxygen species. The electron micrographs of treated cells show a progression towards apoptosis in a majority of the cells. The life span of L1210 leukemia-bearing mice treated with light-exposed MC540 was prolonged compared to the untreated and native MC540 treated mice. High pressure liquid chromatography (HPLC) analysis of light-exposed material shows a completely different elution profile compared to the native compound. Results presented here show that light-exposed photoactive compounds can be used without further illumination and may have significant clinical applications. Photoactive mechanisms dependent on events other than short-lived transient elevations in energy or singlet oxygen must be invoked to explain the reported cytotoxicity.
Gulliya
K S
KS
Baylor Research Foundation, Baylor University Medical Center, Dallas, TX 75226.
Pervaiz
S
S
Dowben
R M
RM
Matthews
J L
JL
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D008027:Light; D051379:Mice; D008811:Mice, Inbred DBA; D011744:Pyrimidinones / Q000494:pharmacology / Q000528:radiation effects* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology*
D011744:Pyrimidinones; C003954:merocyanine dye