In the past five years, it has been reported that certain
dicarboxylic acids (C8-C13) and
azelaic acid (C9) (AZA), in particular, have a remarkable effect in the management of
lentigo maligna, human
malignant melanoma, and certain disorders of
hyperpigmentation. Preclinical trials, therefore, were undertaken in order to evaluate the effectiveness of AZA as a
depigmenting agent and as a chemotherapeutic agent. Twenty-seven uniformly black pigmented guinea pigs were given topical applications of various concentrations (3, 5, 10, 15, and 20%) of AZA preparations for 8 weeks, and their effects on the melanocytes of epilated skin of the backs and the nonepilated ears of guinea pigs were compared to the effects of well-known
depigmenting agents. Whereas
4-isopropylcatechol, monobenzylether of
hydroquinone, monoethylether of
hydroquinone,
hydroquinone, and
4-hydroxyanisole were found to be selectively cytotoxic to melanocytes in black-skinned guinea pigs, AZA has little or no visually recognizable effect on melanocytes in these animals. The
therapeutic effect of local s.c.
injections of various concentrations of AZA preparations on the development of s.c. implanted B-16
melanoma tumor was evaluated in 96 C57BL/6J mice. In addition, 31 BDF1 mice, implanted i.p. with B-16
melanoma tumor, were used to assess the effect of 100-500 mg/kg concentrations of AZA administered i.p. In both studies, AZA revealed no significant tumoristatic or tumoricidal effect on the size, color, and growth of
melanoma. The effect of AZA was also evaluated on S-91A (melanotic or pigmented) and S-91B (amelanotic) human
melanoma cells in culture. Low concentrations (10(-5) and 10(-3) M) of AZA had no inhibitory effect on the growth of these cells. Only at higher concentrations (greater than 10(-3) M) was a cytotoxic effect on cell viability observed. These observations indicate AZA is not selectively cytotoxic to normal and proliferative melanocytes and has no apparent inhibitory effect on the formative process of
melanin pigmentation.