Chawalit ChatupheeraphatChanin NantasenamatKamolchanok DeesrisakSittiruk RoytrakulUsanarat AnurathapanDalina TanyongFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityMahidol UniversityThailand National Center for Genetic Engineering and Biotechnology2020-06-022020-06-022020-01-01EXCLI Journal. Vol.19, (2020), 582-595161121562-s2.0-85084266927https://repository.li.mahidol.ac.th/handle/20.500.14594/56095© 2020, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. 6-gingerol is a traditional medicine that possesses anti-cancer activity against several types of cancer. However, the mechanism of action still remains unclear. Therefore, this study explored the effects of 6-gingerol on anti-leukemic mechanisms in NB4, MOLT4, and Raji leukemic cell. Results indicated that 6-gingerol inhibited cell proliferation and induced cell apoptosis in these 3 cell lines. Moreover, 6-gingerol was shown to increase the mRNA expression of the caspase family thereby suggesting that 6-gingerol induced apoptosis through the caspase-dependent pathway. To explore the signaling pathway regulating 6-gingerol induced apoptosis, we utilized and integrated the network pharmacology approach together with experimental investigations. Targets of 6-gingerol were identified from ChEMBL and STITCH databases, which were used for constructing the protein-protein in-teraction (PPI) network. Results from the PPI network indicated that p53 was a key regulator. Moreover, it was found that 6-gingerol could increase the levels of p53 mRNA in all leukemic cell lines. Thus, 6-gingerol has shown to have anti-cancer activity. In addition, p53, BAX and BCL2 could be involved in the apoptosis pathway of these leukemic cells. This study is anticipated to be useful for the development of 6-gingerol as an anti-leukemic drug in the future.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.17179/excli2019-2008