Cafestol, one of the major compounds in
coffee beans, has been reported for its
tumor cell growth inhibitory activity and anti-carcinogenic activity, although the mechanism of action is poorly understood. In the present study, we investigated the effect of
cafestol on the apoptotic pathway in human renal Caki cells and other
cancer cell lines.
Cafestol treatment inhibited Caki cells viability a dose-dependent manner by inducing apoptosis, as evidenced by DNA fragmentation and the accumulation of sub-G1 phase.
Cafestol-induced apoptosis is associated with the reduction of mitochondrial membrane potential (
MMP), activation of
caspase 3,
cytochrome c release, and down-regulation of
anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1 and cFLIP).
Cafestol-induced apoptosis was blocked by pretreatment with broad
caspase inhibitor
z-VAD-fmk, showing its dependence on
caspases. Ectopic expression of Bcl-2 or Mcl-1 in Caki cells attenuates
cafestol-induced apoptosis. In addition, we have also shown that
cafestol inhibits
phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, and PI3K inhibitor LY29004 significantly increases
cafestol-induced apoptosis in Caki cells. Taken together, our results show the activity of
cafestol to modulate multiple components in apoptotic response of human renal Caki cells and a potential as a therapeutic agent for preventing
cancers such as
renal carcinoma.