title: Tussilago farfara L. augments TRAIL-induced apoptosis through MKK7/JNK activation by inhibition of MKK7‑TIPRL in human hepatocellular carcinoma cells.
abstract: Induction of apoptosis through activation of the TRAIL pathway is considered to be a promising anticancer strategy due to its ability to selectively induce apoptosis in cancer cells. However, the ability of cancer cells to acquire TRAIL resistance has limited the clinical translation of this approach. We previously reported that the TOR signaling pathway regulator-like (TIPRL) protein contributes to the resistance to TRAIL-induced apoptosis by inhibiting the MKK7-c-Jun N-terminal kinase (JNK) pathway via MKK7‑TIPRL interaction. In the present study, we identified Tussilago farfara L. (TF) as a novel TRAIL sensitizer among 500 natural products using an ELISA system that specifically detects the MKK7-TIPRL interaction, and we validated candidates by GST-pull down assay. Co-treatment of Huh7 cells with TF and TRAIL induced apoptosis via inhibition of the MKK7-TIPRL interaction and an increase in MKK7/JNK phosphorylation. This is the first report to describe TF as a novel TRAIL sensitizer, unveiling a potentially novel therapeutic strategy in cancer therapy.
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Hyo-Jung
authors: HJ
authors: Lee
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Hyun-Soo
authors: HS
authors: Cho
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Soo Young
authors: SY
authors: Jun
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Jeong-Ju
authors: JJ
authors: Lee
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Ji-Yong
authors: JY
authors: Yoon
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Jae-Hye
authors: JH
authors: Lee
authors: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Hyuk-Hwan
authors: HH
authors: Song
authors: International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Sang Ho
authors: SH
authors: Choi
authors: International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Soo-Yong
authors: SY
authors: Kim
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Vassiliki
authors: V
authors: Saloura
authors: Han Kang Ltd., Recoleta, Santiago, Chile.
authors: Choon Gil
authors: CG
authors: Park
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors: Nam-Soon
authors: NS
authors: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D031207:Tussilago / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; C577326:TIPRL protein, human