Sphagneticola Trilobata (L.) Pruski (Asteraceae) Methanol Extract Induces Apoptosis in Leukemia Cells through Suppression of BCR/ABL

Abstract

We will study the effects of the methanol extract of Sphagneticola trilobata (L.) Pruski (Asteraceae) (MeST) on the growth of leukemia cells that may contain the BCR/ABL gene. This study also clarifies the mechanism of this effect on these cells. For this purpose, the cells harboring wild-type BCR/ABL, imatinib-resistant BCR/ABL (K562 and TCCYT315I), or Ba/F3 cells transfected with wild-type or mutant BCR/ABL genes were used. The results showed that MeST effectively inhibited the viability of leukemia cells in both a dose- and time-dependent manner. The effect of MeST seems to be more sensitive in the cells that carry imatinib-resistant BCR/ABL (especially the T315I BCR/ABL mutation) than those with wild-type BCR/ABL. Furthermore, we have demonstrated that the death caused by MeST is apoptosis and the treatment with MeST could suppress the expression of BCR/ABL, subsequently altering the downstream cascade of BCR/ABL such as AKT and MAPK signaling. In conclusion, MeST has been able to suppress the growth of leukemia cells harboring BCR/ABL. The mechanism of the anti-leukemic effect of MeST on cells harboring imatinib-resistant BCR/ABL mutations could be due to the disruption of the BCR/ABL oncoprotein signaling cascade.