Multidrug resistance (MDR) is the main obstacle to a successful
chemotherapy of
lung cancer. We tested the potential of
sulfinosine and
curcumin, alone and in combination, for modulating MDR in the human resistant,
non-small cell lung carcinoma cell line (NCI-H460/R). First, we determined the mutational status of the p53 gene in NCI-H460/R cells by PCR-SSCP and
DNA sequencing and identified mutations which could at least partially contribute to the development of the MDR phenotype. The effects of
sulfinosine and
curcumin were studied, both separately and in combination, at the level of cytotoxicity, cell cycle distribution and gene expression.
Sulfinosine displayed dose-dependent growth inhibition in both resistant and control sensitive cell lines, whereas
curcumin considerably inhibited their growth only at relatively high doses. When
sulfinosine was combined with a low dose of
curcumin the drugs exerted a synergistic cytotoxic effect in NCI-H460/R cells. The expression of MDR-related genes mdr1, gst-pi and
topo IIalpha, was altered by
sulfinosine and
curcumin. The most pronounced effect was observed when the agents were applied together.
Sulfinosine and
curcumin caused perturbations in cell cycle distribution in the NCI-H460/R cell line. The combination of the two drugs induced a more pronounced cell cycle arrest in S and G(2)/M in NCI-H460/R cells. Our results show that
sulfinosine and
curcumin overcome MDR in
non-small cell lung carcinoma cell line (NSCLC), especially in combination despite the presence of a mutated p53 gene.