CT‑1042, a novel anticancer agent, exhibits effects by activating p53 and inhibiting survivin.

A novel small molecular compound, 4-ethyl-8-fluoro-hydroxy-9-methoxy-11-methyl-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione (CT-1042) exhibits potent antitumor activity against many tumor cells in vitro. However, the effects and underlying mechanisms of CT-1042 in non-small cell lung cancer (NSCLC) remain unclear. The present study was designed to determine the anticancer properties and underlying molecular mechanisms of CT-1042 in NCI-H460 NSCLC cells. A thiazolyl blue tetrazolium bromide assay (MTT) was performed to evaluate cell viability and flow cytometry was used to analyze apoptosis, mitochondrial membrane potential (MMP) and cell cycle. Real-time quantitative PCR and western blotting were conducted to determine relative mRNA and protein levels. A tumor xenograft experiment was performed to investigate the effects of CT-1042 on tumor growth in vivo. CT-1042 markedly inhibited the proliferation of twelve cancer cell lines, decreased MMP in subject cells and increased caspase-3 activity. Cell cycle analysis indicated that CT-1042 delayed the cell cycle progression during the G2/M phase in a dose-dependent manner. In addition, CT-1042 induced mitochondrial-mediated apoptosis by activating p53 and Bax, as well as inhibiting Bcl-2 and survivin. Finally, CT-1042 significantly suppressed NCI-H460 xenograft tumor growth in vivo, with low systemic toxicity. Collectively, these results revealed that CT-1042 has significant lung anticancer properties.