title: Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation.
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.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Choi
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Oh
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Yang
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D016193:G1 Phase; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D002867:Chromones; D004224:Diterpenes; C549075:LY 290042; D009025:Morpholines; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; C053400:cafestol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3