Laser photochemotherapy with anthracyclines on cultured human squamous carcinoma cells.
A new treatment for cancer has been tested in vitro using light-sensitive anthracyclines followed by laser photoactivation, as described by several investigators. We previously reported 10-fold enhanced laser killing after 2 hours of incubation with daunomycin by cultured human carcinoma cells. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and topoisomerase inhibition. In the present study, daunomycin was incubated for 2 or 24 hours with P3 squamous carcinoma cells to directly compare cytoplasmic vs. nuclear drug targeting before and after KTP-532 laser activation. Monolayer cultures of the P3 cells sensitized with daunomycin for 2 hours, then chilled (4 degree C), and exposed to the KTP laser (532 nm, 94.2 J/cm2) had a 2- to 10-fold increased therapeutic response compared with drug or laser alone when measured by MTT tetrazolium assays. After 24 hours of incubation with daunomycin, the chemotherapeutic response of P3 tumor cells was amplified 2-fold by laser exposure. The results suggest that daunomycin and laser treatment can be combined for improved therapy of human cancer.
Paiva
M B
MB
Division of Head and Neck Surgery, UCLA School of Medicine, Los Angeles, CA 90024-1624, USA.
Saxton
R E
RE
Letts
G
G
Chung
P S
PS
Soudant
J
J
Vanderwerf
Q
Q
Castro
D J
DJ
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053685:Laser Therapy; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D017319:Photosensitizing Agents; D003630:Daunorubicin