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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 <jats:italic>p53<\/jats:italic><jats:sup><jats:italic>Mut<\/jats:italic><\/jats:sup><jats:italic>\/p16<\/jats:italic><jats:sup><jats:italic>Mut<\/jats:italic><\/jats:sup> were the most sensitive to ART, KYSE150 and KYSE180 cells with <jats:italic>p53<\/jats:italic><jats:sup><jats:italic>Mut<\/jats:italic><\/jats:sup><jats:italic>\/p16<\/jats:italic><jats:sup><jats:italic>Nor<\/jats:italic><\/jats:sup> exhibited intermediate responses to ART, and Eca109 cells with <jats:italic>p53<\/jats:italic><jats:sup><jats:italic>Nor<\/jats:italic><\/jats:sup><jats:italic>\/p16<\/jats:italic><jats:sup><jats:italic>Nor<\/jats:italic><\/jats:sup> 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.<\/jats:p>","DOI":"10.1186\/s40001-024-01882-9","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T03:38:30Z","timestamp":1716349110000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antitumour effects of artesunate via cell cycle checkpoint controls in human oesophageal squamous carcinoma cells"],"prefix":"10.1186","volume":"29","author":[{"given":"Linlin","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hsin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"1882_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500371","author":"L Anfosso","year":"2006","unstructured":"Anfosso L, Efferth T, Albini A, Pfeffer U. 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The present study was approved by the Ethics Committee of the National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital. The studies involving animals was also approved by the Animal Ethics Committee of the National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital and were performed in accordance with ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"293"}}