Antiproliferative effects of N-heterocyclic indolyl glyoxylamide derivatives on human lung cancer cells

Background: N-Heterocyclic indolyl glyoxylamide compounds are derived from the antimicrotubule agent D-24851, which exhibits anticancer activity after oral administration. The actions of these compounds on lung cancer cells are still unknown. Here, we investigated the effects of two N-heterocyclic indolyl glyoxylamides, BPR0C259 and BPR0C123, on non-small human lung cancer cells. Materials and Methods: 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the half maximal inhibitory concentration (IC ₅₀), cell viability and radiation response of A549 cells and H1299 cells. Apoptosis was determined by sub-G ₁ ratio, colony formation assay and caspase-3 activation. Cell cycle distribution was detected using flow cytometry. Results: Both compounds were able to inhibit the viability of human lung cancer cells, although the IC ₅₀ of BPR0C123 was lower than that of BPR0C259. Both compounds induced significant sub-G1 and caspase-3 activation as low as 0.1 μM in both cell lines. These effects were independent of p53 activation because the level of serine-15 phosphorylated p53 was not affected after drug treatment. Furthermore, both compounds induced similar levels of G ₂/M phase arrest and radiosensitivity in these lung cancer cells. Conclusion: Current data suggest that N-heterocyclic indolyl glyoxylamides can suppress the proliferation of and potentially increase radiosensitivity of human lung cancer cells.