Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation

Title
Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation
Author(s)
이태진권택규[권택규]최명진[최명진]박은정[박은정]민경진[민경진]양은선[양은선]김영호[김영호]김상현[김상현]최영현[최영현]박종욱[박종욱]오정화[오정화]
Keywords
KAHWEOL; DEATH; MACROPHAGES; EXPRESSION; PATHWAYS; LUNG
Issue Date
201104
Publisher
ELSEVIER IRELAND LTD
Citation
CHEMICO-BIOLOGICAL INTERACTIONS, v.190, no.2-3, pp.102 - 108
Abstract
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 (Bc1-2, Bcl-xL, Mcl-1 and cFLlP). 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/25358http://dx.doi.org/10.1016/j.cbi.2011.02.013
ISSN
0009-2797
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의과대학 > 해부학교실 > Articles
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