Bioinformatics and experimental studies of anti-leukemic activity from 6-gingerol demonstrate its role in p53 mediated apoptosis pathway.

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 interaction (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.