The ERK1/2 (extracellular signal-regulated kinase 1 and 2) pathway, comprising the protein kinases RAF (v-raf-1 murine leukemia viral oncogene homolog 1), MEK1/2 (mitogen-activated protein kinase or ERK kinase 1 and 2) and ERK1/2 is frequently de-regulated in human cancers, due to mutations in RAS or BRAF (v-raf-1 murine leukemia viral oncogene homolog B1).
These results suggest that c-raf-1 is one of the factors involved in Ara-C resistance in leukemia and lend weight to the case for development of anti-cancer therapeutics involving oncogene-targeted antisense oligonucleotides.
In a previous study, we demonstrated that bufalin, which is an active principle of Chinese medicine, chan'su, caused apoptosis in human leukemia U937 cells by anomalous activation of mitogen-activated protein kinase (MAPK) via the signaling pathway of Ras, Raf-1, and MAPK kinase-1.