BACKGROUND: Treatment with @entity2213 (IM) (a @entity669 kinase inhibitor) is the first line of standard care for @entity1 newly diagnosed with @entity1860 . Despite the success of IM and other @entity669 kinase inhibitors (TKIs), @entity1860 ( @entity1860 ) remains largely incurable, and a number of @entity1860 @entity1 die due to @entity1861 mutation-related drug resistance and @entity9638 . 3, 5-Dihydroxy-6, 7, 3'4'-tetramethoxyflavone (DHTMF) is a polymethoxyflavone isolated from Laggera pterodonta which is a herbal medicine used to treat @entity5 in the Chinese folk. In the previous study, we found DHTMF demonstrated good antiproliferative activities against a number of @entity5 cell lines and induced the apoptosis of CNE cells in vitro in a time- and dose-dependent manner while exhibiting low @entity137 in the two normal cell lines Vero and EVC304. The aim of the present study was to evaluate the proliferation inhibition and apoptosis induced by DHTMF alone and in combination with IM in the IM-resistant @entity1860 cell line K562R. METHODS: Cell proliferation was assayed with the cell counting kit-8 (CCK8) method. The apoptosis percentage was determined by flow cytometry (FCM). Mitochondrial transmembrane potential was detected using FCM and confocal laser-scanning microscopy. The level of proteins involved in apoptosis was detected by Western blotting. RESULTS: DHTMF suppressed K562R cell viability in both time- and dose-dependent manners. DHTMF combined with IM enhanced the inhibitory effects and apoptosis in K562R cells as compared with DHTMF alone. DHTMF alone and in combination with IM significantly decreased the mitochondrial membrane potential and increased the levels of cleaved @entity8187 , @entity14544 , @entity522 , and @entity12982 in K562R cells. CONCLUSIONS: We demonstrated that DHTMF could inhibit IM-resistant K562R cell proliferation and induces apoptosis via the intrinsic mitochondrial apoptotic pathway. These results suggest that DHTMF may be a potential therapeutic drug with lower side effects against IM resistance in @entity1860 cells.

A polymethoxyflavone from Laggera pterodonta induces apoptosis in XXXX -resistant K562R cells via activation of the intrinsic apoptosis pathway.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1861 :: ('25', 'Gene') :: ['Abl'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity522 :: ('836', 'Gene') :: ['caspase-3'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity9638 :: ('MESH:D001752', 'Disease') :: ['blast crisis'] @entity14544 :: ('840', 'Gene') :: ['caspase-7'] @entity8187 :: ('842', 'Gene') :: ['caspase-9'] @entity12982 :: ('142', 'Gene') :: ['PARP'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity2213 :: ('MESH:C097613', 'Chemical') :: ['imatinib mesylate'] @entity1860 :: ('MESH:D015464', 'Disease') :: ['CML', 'chronic myeloid leukemia']
@entity2213 :: (MESH:C097613,Chemical) :: ['imatinib']
