ANTIMELANOMA ACTIVITY OF CHLOROQUINE, AN ANTIMALARIAL AGENT WITH HIGH-AFFINITY FOR MELANIN

The antimalarial agent chloroquine is known for high affinity for mela nin. This 4-aminoquinoline derivative was examined for anti-melanoma a ctivity and uptake into melanoma cells. Chloroquine inhibited growth o f cultured melanoma cells; the effect was much greater to a moderately pigmented cell line HMV-II than to a nonpigmented HMV-I. Treatment wi th chloroquine at a dose of 62 mg/kg i.p. for 12 days prolonged by 71% the life span of mice bearing B16 melanoma, while 24-day treatment at 31 mg/kg resulted in a 81% increase in life span. HMV-II cells showed a two-fold increase in uptake of chloroquine as compared with HMV-I c ells. Chloroquine, 24 hr after administration to mice implanted s.c. w ith B16 melanoma, was selectively accumulated in the pigmented tissues , melanoma and eyes. Other nonpigmented tissues such as the liver, lun g, and kidney showed rapid uptake (within 1 hr) and release. These res ults suggest that chloroquine is toxic to pigmented melanoma cells, th e process being partly mediated by binding to melanin.