Objective: To investigate the antimelanogenesis properties of three sesame compounds-sesamol,sesamin and sesamolin via two stages of melanin synthesis vis-`a-vis sunscreen function and enzyme inhibition in melanoma cell line in order to search for altative depigmenting agents. Methods: Antimelanogenic effects of sesame lignans were assessed in SK-MEL2 compared with the reference depigmenting agents, kojic acid and β-arbutin, in order to evaluate:(a)the sunscreen function of sesamol,sesamin and sesamolin by measurement of UV absorbtion property; (b) the inhibition of tyrosinase activity through mushroom and cellular tyrosinase; and (c) the effect on melanin content and melanogenic protein expression(tyrosinase,TRP-1 and TRP-2)by West blot analysis;and(d)the toxicity of sesamol,sesamin and sesamolin to cells using cell cytotoxicity assay. Results: The results showed that sesamin, sesamolin and sesamol exerted satisfiable sunscreen function by absorbed UVB at 290 nm.Sesamol exhibited the highest inhibition of mushroom tyrosinase activity, but lipophilic sesamolin exhibited the highest cellular tyrosinase inhibition (IC50of 1.6 μM) followed by sesamin, sesamol, and kojic acid, respectively.The order from high to low inhibition of melanin pigment was detected in the SK-MEL2 treated with sesamolin, sesamin, sesamol, kojic acid, and β-arbutin, respectively.Sesamolin and sesamin successfully inhibited cellular tyrosinase activity and respectively decreased TRP-1/TRP-2 (36%/15%) and TRP-1 levels (16%), thereby inhibiting melanogenesis via antityrosinase activity. No cytotoxicity to SK-MEL2 or Vero (normal) cell lines was observed at the lignan concentrations that exerted an anti-melanogenic effect. Conclusions: Three sesame lignans prevent melanin synthesis through 2 stages: (a) by blocking melanin-induction and(b)by interrupting melanogenic enzyme production.This study provides evidence that sesamol, sesamin and sesamolin are potential for anti-melanogenesis agents.