Laser dyes for experimental phototherapy of human cancer: comparison of three rhodamines.
The mitochondrial dye Rhodamine 123 (Rh-123) has been shown to be an effective photosensitizer for argon-laser irradiation of some types of human cancer cells in vitro. We reported that 514.5-nm laser illumination of Rh-123 sensitized human melanoma, and squamous carcinoma cells strongly inhibited tumor-cell proliferation as measured by decreased 3H-thymidine (3H-T) uptake in vitro and may eradicate some tumors when grown as transplants in nude mice. However, several other human tumors were resistant to Rh-123 laser therapy in vitro and in vivo. In the current study, it was possible to obtain 100- to 1000-fold increased sensitivity to 514.5-nm laser illumination by replacement of Rh-123 with the cationic rhodamine dyes Rh-3G and Rh-6G. Cell viability was decreased over 95% and 3H-T incorporation reduced at least 80% by laser phototherapy after sensitizing tumor cells with 1 micrograms/mL Rh-123, 0.01 microgram/mL Rh-3G, or 0.001 microgram/mL Rh-6G. However, Rh-123 alone did not decrease 3H-T uptake significantly unless present at over 10- to 100-fold higher levels than Rh-3G, respectively. The tumor cell dye uptake level was measured by N-butanol extraction and absorption scans at 400 to 600 nm. The results revealed that dye uptake was more rapid, and retention of Rh-3G and Rh-6G was 5- to 10-fold higher than for Rh-123 in the human tumor cells. The data suggest that Rh-3G and Rh-6G may be highly sensitive chromophores for laser phototherapy of human cancer cells.
Haghighat
S
S
Division of Head and Neck Surgery (Otolaryngology), UCLA School of Medicine 90024-1624.
Castro
D J
DJ
Lufkin
R B
RB
Fetterman
H R
HR
Castro
D J
DJ
Soudant
J
J
Ward
P H
PH
Saxton
R E
RE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006358:Hot Temperature; D006801:Humans; D053685:Laser Therapy; D008527:Medulloblastoma / Q000188:drug therapy / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D020112:Rhodamine 123; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D012235:Rhodamines; C026188:rhodamine 6G; D020112:Rhodamine 123; C072232:rhodamine 3G