Interferon-α (IFN-α) has been used in the treatment of several cancers, including chronic myeloid leukemia. Artemisinin, a sesquiterpene lactone endoperoxide that exists in several medicinal plants, is a well known anti-malarial agent. We previously reported that artemisinin by itself caused a relatively low level of HL-60 cell differentiation. In this study, we investigated the effects of IFN-α in combination with artemisinin on cell growth and differentiation in HL-60 leukemia cells. Combination of IFN-α and artemisinin synergistically induced the levels of leukemia cell differentiation, although IFN-α by itself did not affect cell proliferation and differentiation. The increased cell differentiation by IFN-α and artemisinin was significantly suppressed by the inhibitors for protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and jun N-terminal kinase (JNK), but not by the inhibitors for phosphatidylinositol 3-kinase (PI3-K) and p38 mitogen-activated protein kinase (MAPK). Furthermore, co-treatment with IFN-α increased levels of PKCα and phosphorylated ERK. Taken together, these results indicate the enhancement of artemisinin-induced HL-60 cell differentiation by IFN-α through the activation of a PKCα/ERK signaling pathway, and suggest a possible use of IFN-α and artemisinin in the treatment of leukemic diseases.
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