POTENCY AND SELECTIVE TOXICITY OP TETRA(HYDROXYPHENYL)PORPHYRINS AND TETRAKIS(DIHYDROXYPHENYL)PORPHYRINS IN HUMAN-MELANOMA CELLS, WITH AND WITHOUT EXPOSURE TO RED-LIGHT
Da. James et al., POTENCY AND SELECTIVE TOXICITY OP TETRA(HYDROXYPHENYL)PORPHYRINS AND TETRAKIS(DIHYDROXYPHENYL)PORPHYRINS IN HUMAN-MELANOMA CELLS, WITH AND WITHOUT EXPOSURE TO RED-LIGHT, Photochemistry and photobiology, 59(4), 1994, pp. 441-447
A series of tetra(hydroxyphenyl)-(2-, 3- and 4-hydroxy; THPP) and tetr
akis(dihydroxyphenyl)porphyrins (2,3-, 2,4-, 2,5-, 3,4-, and 3.5-dihyd
roxy; TDHPP) was synthesized and tested for toxicity in HeLa cells and
human melanoma cell lines. Irradiation of drug-treated cells with >60
0 nm light greatly increased the toxicity of all drugs except the 2,5-
and 3,5-TDHPP. The THPP were more toxic than TDHPP in all cell lines,
with or without irradiation; of the dihydroxy derivatives, the 3,4- a
nd 2,4-isomers were the most toxic and the 2,5-isomer was the least to
xic. The MM96E melanoma cell line, shown previously to be sensitive to
hydrogen peroxide and superoxide ion, was not hypersensitive to killi
ng by any of the above agents. HeLa cells, which lacked glutathione-S-
transferase activity, were sensitive to the 4- and 2,3-isomers after i
rradiation; similar amounts of all drugs were taken up by HeLa cells.
The pigmented melanoma cell line MM418, resistant to UV-B and in situ-
generated hydrogen peroxide but sensitive to glutathione (GSH) depleti
on, was found to be resistant to the 2,3-isomer (no irradiation) and s
ensitive to the 3,4-isomer. The results indicate that (1) phototoxicit
y in these phenylporphyrins is not mediated by superoxide ions or hydr
oxyl radicals, (2) toxicity is dependent on the orientation of the hyd
roxy groups, (3) GSH transferase and possibly GSH itself offer protect
ion from the 4- and 3,4-derivatives, respectively, and (4) the 3,4-der
ivative and analogues of similar selectivity should be evaluated furth
er for the treatment of primary melanoma.