Thalidomide （α-N-phthalimido-glutarimide, TLD） is a kind of anti-angiogenic and anti-inflammatory drug, and showed effects in the treatment of several disease entities. In this study, the biological effects of a novel N-sugar substituted phthalimide （STA-35） on the regulation of multidrug resistance （MDR） to doxorubicin （ADR） were investigated. The proliferation of cancer cells was detected by a SRB assay. The activity of P-glycoprotein （P-gp） was determined by a Flow cytometry. The expression of P-gp was measured by western blotting. The results showed that STA-35 inhibited the proliferation of human breast cancer cell line MCF-7 and its ADR resistant cell line MCF-7/ADR, and the relative resistance was only 1.19. Meanwhile, STA-35 could sensitize the cytotoxicity of ADR in MCF-7/ADR cells. In addition, we found that STA-35 reduced the activity of P-gp by suppressing the P-gp expression, which was indicated by the increase in the accumulation of rhodamine 123 in MCF-7/ADR cells. These results suggested a promising application of STA-35 as the MDR reversing agent. The underlying mechanism of the effects might be attributed to the inhibition of P-gp.
Allicin, a major biologically active component of garlic, is produced from its inactive precursor aUiin by the enzyme alliinase. In this study, we investigated its effects on human nasopharyngeal carcinoma KB cells. After incubation for 48 h, allicin inhibited the growth of KB cells in a concentration-dependent manner with an IC50 value of （2.2±0.2） μg/mL. Incubation with allicin for 48 h caused a concentration-dependent induction of apoptosis in the concentration range of （16-48） μg/mL, and the induction of apoptosis was confirmed by the changes of mitochondrial membrane potential, F-actin contents and nuclear condensation in KB cells. Moreover, allicin concentration-dependently arrested KB cells at the S-phase of the cell cycle in the range of （16-48） μg/mL. In addition, treatment with the compound caused concentration-dependent disassembly of microtubule cytoskeleton in KB cells, which is similar to the effect of colchicine, a well-known microtubule destabilizing agent. We concluded that the abilities of allicin to inhibit the proliferation of KB cells probably relate to its apoptosis induction, cell cycle arrest and microtubule destabilizing properties.
