title: Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.
abstract: TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy. © 2015 Wiley Periodicals, Inc.
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.|Department of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
authors: Ji-Yong
authors: JY
authors: Yoon
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: Hyun-Soo
authors: HS
authors: Cho
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: Jeong-Ju
authors: JJ
authors: Lee
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: Hyo-Jung
authors: HJ
authors: Lee
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors: Soo Young
authors: SY
authors: Jun
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors: Jae-Hye
authors: JH
authors: Lee
authors: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: Hyuk-Hwan
authors: HH
authors: Song
authors: International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: SangHo
authors: S
authors: Choi
authors: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois.
authors: Vassiliki
authors: V
authors: Saloura
authors: Han Kang Ltda, Santiago, Chile.
authors: Choon Gil
authors: CG
authors: Park
authors: Department of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
authors: Cheol-Hee
authors: CH
authors: Kim
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors: Nam-Soon
authors: NS
authors: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D048688:MAP Kinase Kinase 7 / Q000378:metabolism; D060066:Protein Interaction Maps / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000494:pharmacology*; D031205:Taraxacum / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047908:Intracellular Signaling Peptides and Proteins; C577326:TIPRL protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human
keywords: HCC; TIPRL; TRAIL resistance; Taraxacum officinale F.H. Wigg; apoptosis