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Based on our previous findings considering the anti\u2010leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti\u2010cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti\u2010leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL\/6 nude mice, and the anti\u2010leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6\u2010shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti\u2010neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh\u2010mediated apoptosis in Nalm\u20106 cells confirmed by Western blotting and RT\u2010PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti\u2010leukaemic role of ginger extract, promoted by MTX. Moreover, 6\u2010shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.<\/jats:p>","DOI":"10.1111\/jcmm.16528","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T15:20:28Z","timestamp":1620055228000},"page":"6148-6160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["6\u2010Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species"],"prefix":"10.1111","volume":"25","author":[{"given":"Somayeh","family":"Najafi Dorcheh","sequence":"first","affiliation":[{"name":"University of Isfahan Isfahan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-255X","authenticated-orcid":false,"given":"Soheila","family":"Rahgozar","sequence":"additional","affiliation":[{"name":"University of Isfahan 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