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Oncol Rep. 2014 Sep;32(3):1117-23. doi: 10.3892/or.2014.3279. Epub 2014 Jun 23.

Tussilago farfara L. augments TRAIL-induced apoptosis through MKK7/JNK activation by inhibition of MKK7‑TIPRL in human hepatocellular carcinoma cells.

Author information

  • 1Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
  • 2Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
  • 3International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
  • 4Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
  • 5Han Kang Ltd., Recoleta, Santiago, Chile.

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.

[PubMed - indexed for MEDLINE]
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