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.
Paiva
M B
MB
Department of Surgery, UCLA School of Medicine, Los Angeles, California 90095-1794, USA.
Saxton
R E
RE
Graeber
I P
IP
Jongewaard
N
N
Eshraghi
A A
AA
Suh
M J
MJ
Paek
W H
WH
Castro
D J
DJ
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