Reversion of P-glycoprotein-mediated multidrug resistance by diallyl trisulfide in a human osteosarcoma cell line.

Abstract

Diallyl trisulfide (DATS), the main sulfuric compound in garlic, has been shown to have antitumor effects. The present study aimed to ascertain whether DATS reverses the drug resistance of human osteosarcoma cells in vitro and to investigate its potential mechanisms. Human osteosarcoma U2-OS cells were treated with different concentrations of DATS. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while P-glycoprotein (P-gp) expression and the proportion of apoptotic cells were measured by flow cytometry. Morphological changes were observed under an optical microscope. Νuclear factor-κB (NF-κB) and inhibitor of NF-κB (IκB) activities were measured by PCR and western blot analysis. Results showed that the proliferation of U2-OS cells treated with different concentrations of DATS was significantly decreased in a concentration- and time-dependent manner. DATS increased the toxic effect of adriamycin on U2-OS cells. Moreover, P-gp expression was decreased and the apoptosis rate was increased in a concentration-dependent manner following treatment of DATS. Additionally, NF-κB activity was inhibited by DATS while expression of IκB was increased. Our data clearly suggest that DATS has significant anticancer effects on human osteosarcoma cells. The potential mechanisms include reducing the multidrug resistance and inducing apoptosis. NF-κB suppression may be involved in DATS-induced inhibition of cell proliferation.