Abstract
In previous research, the authors demonstrated that the methanol extract of Artemisia vulgaris (AVM) has the ability to inhibit chronic myeloid leukemia (CML) cell proliferation. The aim of the present study was to determine and clarify the mechanism of action of AVM. BCR/ABL activation is present in >90% of CML cases. As a result, cells expressing different forms of BCR/ABL were recruited for the present study, including K562 (human wild-type) or TCCY-T315I (human imatinib-resistant) and the Ba/F3-(T315I/E279K/Y253H) (mouse BCR/ABL point mutation-transfected cells). The results revealed that AVM inhibited the phosphorylation of BCR/ABL and their subsequent molecular signals including AKT and MAPK activation. AVM induced the release of cleaved PARP and cleaved caspase-3 caused apoptosis and inhibited the viability of these cells. Interestingly, AVM appeared to be more sensitive to imatinib-resistant (T315I, Y253H, and E279K) than wild-type BCR/ABL cells, indicating its potential to overcome imatinib-resistant severe issues in CML. Moreover, the effects of various sub-fractions of AVM were then investigated in order to determine the optimal solvent for the identification of anticancer bioactive compounds. The results demonstrated that the ethyl acetate and chloroform fractions were more effective than the n-hexane and water fractions. It is thus concluded that AVM inhibits the activity of BCR/ABL and their subsequent molecular signals, including AKT and MAPK, resulting in cytotoxicity via apoptosis.