Role of L-Type Amino Acid Transporter 1 (LAT1) for the Selective Cytotoxicity of Sesamol in Human Melanoma Cells.

Sesamol is effective against melanoma cells with less damage to normal cells. The underlying selective cytotoxicity of sesamol in melanoma vs. non-cancerous cells is undefined. Melanoma cells differ from normal cells by over-expression of the L-type amino acid transporter 1 (LAT1). We sought to clarify the transport mechanism on selective cytotoxicity of sesamol in melanoma cells. A human melanoma cell line (SK-MEL-2) and African monkey epithelial cell line (Vero) were used to study the cellular uptake and cytotoxicity of sesamol. The intracellular concentration of sesamol was quantified by UV-HPLC. The cytotoxicity was determined by neutral red uptake assay. Sesamol showed a higher distribution volume and uptake clearance in SK-MEL-2 than Vero cells. Sesamol was distributed by both carrier-mediated and passive transport by having greater carrier-mediated transport into SK-MEL-2 cells than Vero cells. Higher mRNA expression and function of LAT1 over LAT2 were evident in SK-MEL-2 cells compared to Vero cells. Sesamol uptake and sesamol cytotoxicity were inhibited by the LAT1 inhibitor, suggesting LAT1 had a role in sesamol transport and its bioactivity in melanoma. The LAT1-mediated transport of sesamol is indicative of how it engages cytotoxicity in melanoma cells with promising therapeutic benefits.