Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonylureido-carnosine in a human epithelial cell line.

The aim of the present study was to evaluate whether the transepithelial transport of the anticancer compound 4-toluenesulfonylureido-carnosine (Ts-carnosine) and the dipeptide moiety L-carnosine was due to a hPepT1 carrier-mediated flux.Transport experiments were conducted using Caco-2 cell monolayers and either reversed-phase HPLC-UV or liquid scintillation counting methods for quantification. pKa, LogD, and LogP were determined using the Sirius GlpKa meter.L-carnosine was transported across the apical membrane with a Km,app of 2.48 +/- 1.16 mM and a Vmax of 2.08 +/- 0.34 nmol x cm(-2) x min(-1) and across the basolateral membrane with a Km,app of 7.21 +/- 3.17 mM and a Vmax of 0.54 +/- 0.10 nmol x cm(-2) x min(-1), and transepithelially with a Papp of 4.46 x 10(-2) +/- 6.4 x 10(-6) cm x min(-10). Ts-carnosine had an affinity (Ki) for hPepT1 of 2.33 +/- 0.54 mM; however, the transepithelial transport was low as compared to that of L-carnosine.L-carnosine was transported across both the apical and basolateral membrane of Caco-2 cell monolayers in a carrier-mediated manner however, the transepithelial transport followed apparent simple non-saturable kinetics. Ts-carnosine had an affinity for hPepT1 but a relatively low transepithelial transport. This indicates that the transepithelial transport of L-carnosine and Ts-carnosine is not hPepT1 carrier-mediated and that L-carnosine is not a suitable dipeptide moiety for hPepT1-mediated absorption of sulfonamide-type anticancer compounds.