How does artemisinin act inside a cell?

Zhong, Mengjiao; Zhou, Bing

doi:10.1360/n972017-00194

Cited by 2 publications

(1 citation statement)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Artemisinin, a sesquiterpene lactone isolated from the Chinese medicinal plant Sweet Wormwood ( Artemisia annua L., Asteraceae ), is an effective antimalarial drug [ 35 ]. When artemisinin interacts with haem and/or iron, the endoperoxide moiety of artemisinin is cleaved to generate reactive oxygen species (ROS) that exert toxic effects on Plasmodium [ 34 , 37 ]. Thus, the endoperoxide moiety inside artemisinin is crucial for its biological effects.…”

Section: Introductionmentioning

confidence: 99%

Antitumour effects of artesunate via cell cycle checkpoint controls in human oesophageal squamous carcinoma cells

Mao,

Deng,

et al. 2024

Eur J Med Res

View full text Add to dashboard Cite

Artesunate (ART), an effective antimalarial semisynthetic derivative of artemisinin, exhibits antitumour properties, but the mechanism(s) involved remain elusive. In this study, we investigated the antitumour effects of ART on human oesophageal squamous cell carcinoma (ESCC) cell lines. Treatment of ESCC cell lines with ART resulted in the production of excessive reactive oxygen species (ROS) that induced DNA damage, reduced cell proliferation and inhibited clonogenicity via G1-S cell cycle arrest and/or apoptosis in vitro. The administration of ART to nude mice with ESCC cell xenografts inhibited tumour formation in vivo. However, the cytotoxicity of ART strongly differed among the ESCC cell lines tested. Transcriptomic profiling revealed that although the expression of large numbers of genes in ESCC cell lines was affected by ART treatment, these genes could be functionally clustered into pathways involved in regulating cell cycle progression, DNA metabolism and apoptosis. We revealed that p53 and Cdk4/6-p16-Rb cell cycle checkpoint controls were critical determinants required for mediating ART cytotoxicity in ESCC cell lines. Specifically, KYSE30 cells with p53Mut/p16Mut were the most sensitive to ART, KYSE150 and KYSE180 cells with p53Mut/p16Nor exhibited intermediate responses to ART, and Eca109 cells with p53Nor/p16Nor exhibited the most resistance to ATR. Consistently, perturbation of p53 expression using RNA interference (RNAi) and/or Cdk4/6 activity using the inhibitor palbociclib altered ART cytotoxicity in KYSE30 cells. Given that the p53 and Cdk4/6-cyclin D1-p16-Rb genes are commonly mutated in ESCC, our results potentially shed new light on neoadjuvant chemotherapy strategies for ESCC.

show abstract

Section: Introductionmentioning

confidence: 99%