Previously, we reported that
acetaminophen (
APAP) showed selective toxicity towards
melanoma cell lines. In the current study, we investigated further the role of
tyrosinase in
APAP toxicity in SK-MEL-28
melanoma cells in the presence of a
short hairpin RNA (
shRNA) plasmid, silencing
tyrosinase gene. Results from
tyrosinase shRNA experiments showed that
APAP led to negligible toxicity in
shRNA plasmid-treated cells. It was also found that
APAP selectively caused escalation in
reactive oxygen species (ROS) formation and intracellular GSH (ICG) depletion in melanocytic human SK-MEL-28 and murine B16-F0
melanoma cells that express functional
tyrosinase whereas it lacked significant effects on ROS formation and ICG in amelanotic C32
melanoma cells that do not express functional
tyrosinase. These findings suggest that
tyrosinase plays a major role in
APAP selective induced toxicity in melanocytic
melanoma cell lines. Furthermore, the in vivo efficacy and toxicity of
APAP in the skin
melanoma tumor model in mice was investigated. Mice receiving
APAP at 60, 80, 100 and 300 mg/kg/day, day 7 through 13 post
melanoma cell inoculation demonstrated
tumor size growth inhibition by 7+/-14, 30+/-17, 45+/-11 and 57+/-3%, respectively. Mice receiving
APAP day 1 through 13 post
melanoma cell inoculation showed
tumor size growth inhibition by 11+/-7, 33+/-9, 36+/-20 and 44+/-28%, respectively.