Mechanism of antitumoral activity of catechols in culture.
Cell lines Raji and K 562, lacking tyrosinase, and two melanotic human melanoma cell lines (IRE 1 and IRE 2), were exposed to concentrations from 5 X 10(-3) M to 10(-5) M of different phenols which are substrates of tyrosinase, i.e. l-dopa, dopamine, hydroquinone, terbutylcatechol, and of phenols which are not substrates of the tyrosinase, i.e. resorcinol, butylated hydroxyanisole and hydroquinone dimethyl ether. Cultures were carried out in the presence or in the absence of oxygen radical scavenger enzymes superoxide dismutase, catalase and peroxidase. The stability of each substance in culture medium was assayed by high performance liquid chromatography (HPLC). Results showed that: catechols which are substrates of tyrosinase decompose fully after 24 hr in medium; they are equally toxic for melanoma and non-melanoma cell lines; their toxicity increases when they are preincubated in medium for 24 hr and 48 hr before addition of cells; their toxicity is significantly reduced by addition of scavenger enzymes; on the contrary, phenols not substrates of tyrosinase are stable in medium and their toxicity is not reduced by scavenger enzymes. It is concluded that tyrosinase does not play a major role in catechol toxicity in vitro, which is probably due to some products of catechol decomposition, especially oxygen radicals, acting outside the cells.
D000840:Anisoles; D002083:Butylated Hydroxyanisole / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002396:Catechols / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D012118:Resorcinols / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000840:Anisoles; D002396:Catechols; D003470:Culture Media; D006873:Hydroquinones; D012118:Resorcinols; C031200:1,4-dimethoxybenzene; D002083:Butylated Hydroxyanisole; D007980:Levodopa; C015047:p-tert-butyl catechol; D010544:Peroxidases; D002374:Catalase; D014442:Monophenol Monooxygenase; D013482:Superoxide Dismutase; C031927:hydroquinone; C031389:resorcinol