Psoralen derivatives and longwave ultraviolet irradiation are active in vitro against human melanoma cell line.
Cutaneous malignant melanoma is a very serious form of skin cancer that arises from melanocytes. Currently there is no effective treatment for metastatic melanoma so intense clinical trials are evaluating new drugs for this human malignancy. Psoralens are a group of compounds that bind to DNA in rapidly dividing cells and with ultraviolet light in the A band (UVA) cause DNA crosslinking, thereby preventing cellular division. They are used in the treatment of psoriasis and cutaneous T-cell lymphoma among other skin and blood diseases. We have investigated the cytotoxic potential of three psoralen derivatives plus UVA exposure (PUVA) on a established cell line of human melanoma. Cells were treated with different concentrations of 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP) and 7-methylpyridopsoralen (MPP), for 1 h and after exposure to UVA light (0.3 J/cm(2)) were allowed to recover over a 24-72 h period. Viability was assessed by the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Cisplatin, one of the most important drugs in the chemotherapy of melanoma, was included for comparative studies. All the psoralen derivatives tested were markedly cytotoxic in a dose and post-exposure-time dependent manner. The IC(50) values for 72 h of post-exposure time were as follows: MPP=0.05+/-0.01, TMP=0.13+/-0.003 and 8-MOP=10.79+/-1.85 micromol/L. Regardless of the limitations of the in vitro model, our results suggested that the lower IC(50) values of TMP and MPP might be of clinical importance.
Physiological Sciences Department, Federal University of Goiás, 74001-970 Goiânia, Brazil.
Vanessa
V
Carneiro Leite
Raquel
R
Ferreira Santos
Lee
L
Chen Chen
Lidia
L
Andreu Guillo
D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D003124:Colorimetry / Q000379:methods; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000494:pharmacology*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008730:Methoxsalen / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology; D013778:Tetrazolium Salts / Q000032:analysis; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D011564:Furocoumarins; D017319:Photosensitizing Agents; D013778:Tetrazolium Salts; D004247:DNA; D002945:Cisplatin; D008730:Methoxsalen