title: Thymoquinone induces apoptosis through downregulation of c-FLIP and Bcl-2 in renal carcinoma Caki cells.
abstract: Renal carcinoma is a common and frequently fatal carcinoma occurring worldwide and death rates due to this carcinoma are increasing with time. In the present study, we investigated the potential of thymoquinone a natural compound to induce apoptosis in renal carcinoma Caki cells. Thymoquinone efficiently enhanced the apoptotic population of Caki cells in a dose-dependent manner. Moreover, thymoquinone-mediated apoptosis caused downregulation of c-FLIP and Bcl-2, the master regulators of the anti-apoptotic mechanism. However, we did not find any changes in mRNA expression level of c-FLIP, therefore; this regulation of c-FLIP was a result of post-translation modification by thymoquinone. In contrast, expression of the Bcl-2 protein was observed at both transcriptional and translational level. However, we also observed that thymoquinone enhanced the level of intracellular reactive oxygen species (ROS) in Caki cells, which resulted in reduction of mitochondrial membrane potential (MMP) and cytochrome c release into cytoplasm. Our results postulate that thymoquinone induces apoptosis through downregulating c-FLIP and Bcl-2 which can be utilized as a chemotherapeutic agent to treat renal carcinoma.
authors: Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors: Eun Jung
authors: EJ
authors: Park
authors: Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors: Anil Kumar
authors: AK
authors: Chauhan
authors: Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors: Kyoung-Jin
authors: KJ
authors: Min
authors: Department of Hotel Cuisine and Food Service Management, Gimcheon University, Gimcheon 39528, Republic of Korea.
authors: Dong Cheol
authors: DC
authors: Park
authors: Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors: Taeg Kyu
authors: TK
authors: Kwon
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000008:administration & dosage*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D045304:Cytochromes c; C003466:thymoquinone