The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells through down-regulation of Akt phosphorylation and activation of JNK
- 박종욱; 권택규
- Alternative Author(s)
- Park, Jong Wook; Kwon, Taeg Kyu
- Publication Year
- Kahweol, the coffee-specific diterpene, has
been reported for its tumor cell growth inhibitory activity
and anti-carcinogenic activity. The mechanism by which
kahweol initiates apoptosis remains poorly understood. In
the present study, we investigated the effect of kahweol on
the apoptotic pathway in U937 human promonocytic cells.
We show that kahweol induces apoptosis in association
with the activation of caspase 3 and cytochrome c release
from the mitochondria to the cytosol, as well as downregulation
of anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1
and XIAP). Kahweol altered the phosphorylation state of
members of the MAPKs and Akt. Ectopic expression of
Bcl-2 or constitutive active Akt (myr-Akt) in U937 cells
attenuates kahweol-induced apoptosis. In addition, we have
also shown that JNK and Akt signal pathway plays a crucial
role in kahweol-induced apoptosis in U937 cells.
Taken together, our results show the activity of kahweol to
modulate multiple components in apoptotic response of
human leukemia cells and raise the possibility a novel
therapeutic strategy in hematological malignancies.
Keywords Kahweol Apoptosis pAkt U937
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