Improved photochemotherapy of malignant cells with daunomycin and the KTP laser.
Laser photochemotherapy of malignancies may become an effective palliative treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fiberoptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhanced cytotoxicity after exposure to argon laser light at 514 nm. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and daunomycin topoisomerase inhibition. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochromatic green-wavelength light. Drug uptake and laser energy levels were optimized for maximum synergy. To test light-enhanced chemotherapy in vitro, the kinetics of cell uptake and toxicity of daunomycin was measured at 1, 2, and 5 microg/ml in three human tumor cell lines: P3 squamous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exposure to 300- to 900-nm visible light from a xenon lamp or monochromatic 532-nm green light from a KTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear phototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxicity is enhanced when exposed to 532-nm laser illumination in the three tumor types tested and confirm that the response is related to both energy level and drug dose.
Department of Surgery, UCLA School of Medicine, Los Angeles, California 90095-1794, USA.
M B
MB
Paiva
R E
RE
Saxton
I P
IP
Graeber
N
N
Jongewaard
A A
AA
Eshraghi
M J
MJ
Suh
W H
WH
Paek
D J
DJ
Castro
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D003630:Daunorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053685:Laser Therapy; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D010166:Palliative Care; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D017319:Photosensitizing Agents; D003630:Daunorubicin