2. Academic Validation
  3. Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite

Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite

  • Sci Rep. 2019 Oct 29;9(1):15528. doi: 10.1038/s41598-019-52108-6.
Yan Zhu 1 2,  Christian Klausen 3,  Jieyun Zhou 4,  Xiangjie Guo 4,  Yu Zhang 5,  Hua Zhu 3,  Zhao Li 4,  Jung-Chien Cheng 3,  Shuwu Xie 4,  Wenjie Yang 4,  Ying Li 5,  Peter C K Leung 6
Affiliations

Affiliations

  • 1 Laboratory of Reproductive Pharmacology, Shanghai Institute of Planned Parenthood Research; Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China. zhuyan@sippr.org.
  • 2 Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. zhuyan@sippr.org.
  • 3 Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
  • 4 Laboratory of Reproductive Pharmacology, Shanghai Institute of Planned Parenthood Research; Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China.
  • 5 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 6 Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. peter.leung@ubc.ca.
PMID: 31664127 DOI: 10.1038/s41598-019-52108-6
Abstract

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 inhibition rates ranged from 35.8% to 49.9%, respectively, after 2.5 and 5.0 mg/kg SM1044 intraperitoneal treatment, and no obvious behavioural and histopathological abnormalities were observed in SM1044-treated mice in this context. SM1044 predominantly accumulated in the uteri of mice after a single injection. SM1044 displayed efficacy as a tumour suppressor with distinct mechanism of action and unique tissue distribution, properties that distinguish it from Other artemisinin analogues. Our findings provide a new clue for artemisinin analogue against Cancer.

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