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
Authors
Min Jung ChoiEun Jung ParkJung Hwa OhKyoung-Jin MinEun Sun YangYoung Ho KimTae Jin LeeSang Hyun KimYung Hyun ChoiJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
박종욱; 권택규
Department
Dept. of Immunology (면역학)
Issue Date
2011
Publisher
School of Medicine
Citation
Chemico-Biological Interactions, Vol.190(2-3) : 102-108, 2011
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 (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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/17052
ISSN
0009-2797
Appears in Collections:
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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