biostudies-literatureZhu YChina Scholarship CouncilScience and Technology Commission of Shanghai MunicipalityScience and Technology Climbing Fund of SIPPRCAS | State Key Laboratory of Drug ResearchCIHR15528https://www.ebi.ac.uk/biostudies/studies/S-EPMC6820742biostudies-literatureUnknown9(1)In the present study, a novel dimer, SM1044, selected from a series of dihydroartemisinin (DHA) derivatives containing nitrogen atoms comprising simple aliphatic amine linkers, showed strong growth inhibition in six types of human endometrial cancer (EC) cells, with half maximal inhibitory concentration (IC₅₀) and 95% confidence interval (CI) < 3.6 (1.16~11.23) μM. SM1044 evoked apoptosis and activated caspase-3, -8 and -9 in a concentration- and time-dependent manner, and these effects were manifested early in RL95-2 compared to KLE cells, possibly correlated with the induction of intracellular ONOO^-. Catalase and uric acid attenuated the growth inhibitory effects of SM1044 on EC cells, but sodium pyruvate did not. In vivo, the average xenograft tumour growth inhibitScientific reportsNovel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite.PMC6820742#14431901900#SIMM1903KF-11143317#201508310018Yang WLi YLi ZZhu YGuo XZhang YKlausen CZhu HLeung PCKCheng JCXie SZhou JfalseNovel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite.In the present study, a novel dimer, SM1044, selected from a series of dihydroartemisinin (DHA) derivatives containing nitrogen atoms comprising simple aliphatic amine linkers, showed strong growth inhibition in six types of human endometrial cancer (EC) cells, with half maximal inhibitory concentration (IC₅₀) and 95% confidence interval (CI) < 3.6 (1.16~11.23) μM. SM1044 evoked apoptosis and activated caspase-3, -8 and -9 in a concentration- and time-dependent manner, and these effects were manifested early in RL95-2 compared to KLE cells, possibly correlated with the induction of intracellular ONOO^-. Catalase and uric acid attenuated the growth inhibitory effects of SM1044 on EC cells, but sodium pyruvate did not. In vivo, the average xenograft tumour growth inhibit2019-01-01T00:00:00Z2019 Oct2025-04-05T13:30:34.426Z2019-11-12T08:06:03ZS-EPMC68207423166412710.1038/s41598-019-52108-6