Abstract
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.
Highlights
Most small molecules are transported across cell membranes via passive transport and/or carriermediated transport [1,2,3,4]
Carrier-mediated proteins overexpressed in melanoma cells include L-type amino acid transporter 1 (LAT1/SLC7A5) [5,6,7], L-type amino acid transporter 2 (LAT2/SLC7A8) [5,6,7], alanine-serine-cysteine transporter 2 (ASCT2/SLC1A5) [5,6,7], and glucose uptake transporter 1 (GLUT1) [8]
Sesamol distribution into the SK-MEL-2 and Vero cells at 37 ◦ C occurred in a time-dependent manner (Figure 1A,B, solid line)
Summary
Most small molecules are transported across cell membranes via passive transport and/or carriermediated transport [1,2,3,4]. Carrier-mediated transporters are key determinants for pharmacokinetic, safety, and efficacy profiles of small molecules [4]. Carrier-mediated proteins overexpressed in melanoma cells include L-type amino acid transporter 1 (LAT1/SLC7A5) [5,6,7], L-type amino acid transporter 2 (LAT2/SLC7A8) [5,6,7], alanine-serine-cysteine transporter 2 (ASCT2/SLC1A5) [5,6,7], and glucose uptake transporter 1 (GLUT1) [8]. LAT1 is used as a biomarker for disease progression in malignant melanoma patients [6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
