TY - JOUR
T1 - Interferon-α enhances artemisinin-induced differentiation of HL-60 leukemia cells via a PKCα/ERK pathway
AU - Kim, Seung Hyun
AU - Chun, Sang Young
AU - Kim, Tae Sung
N1 - Funding Information:
This study was supported by a grant from the Basic Research Program of the Korea Science & Engineering Foundation (RO1-2005-000-10459-0), and in part by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ10-PG6-01GN16-0005).
PY - 2008/6/10
Y1 - 2008/6/10
N2 - 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.
AB - 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.
KW - Artemisinin
KW - Differentiation
KW - Interferon-α
KW - Leukemia
UR - http://www.scopus.com/inward/record.url?scp=44149122802&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2008.03.036
DO - 10.1016/j.ejphar.2008.03.036
M3 - Article
C2 - 18456255
AN - SCOPUS:44149122802
SN - 0014-2999
VL - 587
SP - 65
EP - 72
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -
