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.
Highlights
Tudorel OlaruChronic myeloid leukemia (CML) is a type of cancer found in the blood and bone marrow
The result showed that methanol extract of S.trilobata (MeST) could suppress the growth of human leukemic K562 cells as well as TCCY-T315I cells in a dose-dependent manner (Figure 1)
The results showed that the selectivity index (SI) values of MeST were higher than 3 (Table 1 and Figure 3B), indicating that the MeST had potent cytotoxic activity and good selectivity against leukemia cells with BCR/ABL
Summary
Chronic myeloid leukemia (CML) is a type of cancer found in the blood and bone marrow. This disease is characterized by a reciprocal t(9;22) chromosomal translocation, resulting in the formation of the Philadelphia (Ph) chromosome containing the BCR/ABL gene [1]. CML patients have the benefit of treatment due to the introduction of imatinib, a tyrosine kinase inhibitor (TKI) [2]. The imatinib resistance emerged as a serious problem. As least four generations of TKIs have been developed and shown to be potentially effective in treatment [3]. Not all the TKI resistance problems are solved
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