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.