Phospho-
sulindac (PS) is a safe
sulindac derivative with promising anticancer efficacy in
colon cancer. We evaluated whether its combination with
curcumin could enhance the efficacy in the treatment of
lung cancer.
Curcumin, the principal bioactive component in turmeric, has demonstrated versatile capabilities to modify the therapeutic efficacy of a wide range of
anticancer agents. Here, we evaluated the effect of co-administration of
curcumin on the anticancer activity of PS in a mouse xenograft model of human
lung cancer.
Curcumin enhanced the cellular uptake of PS in human lung and
colon cancer cell lines. To assess the potential synergism between
curcumin and PS in vivo,
curcumin was suspended in 10% Tween-80 or formulated in micellar nanoparticles and given to mice by oral gavage prior to the administration of PS. Both formulations of
curcumin significantly improved the pharmacokinetic profiles of PS, with the 10% Tween-80
suspension being much more effective than the nanoparticle formation. However,
curcumin did not exhibit any significant modification of the metabolite profile of PS. Furthermore, in a mouse subcutaneous xenograft model of human
lung cancer, PS (200 mg/kg) in combination with
curcumin (500 mg/kg) suspended in 10% Tween-80 (51% inhibition, p<0.05) was significantly more efficacious than PS plus
micelle curcumin (30%) or PS (25%) or
curcumin alone (no effect). Consistent with the improved pharmacokinetics, the combination treatment group had higher levels of PS and its metabolites in the xenografts compared to PS alone. Our results show that
curcumin substantially improves the pharmacokinetics of PS leading to synergistic inhibition of the growth of human
lung cancer xenografts, representing a promising
drug combination.