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Mol Carcinog. 2016 Apr;55(4):387-96. doi: 10.1002/mc.22288. Epub 2015 Feb 3.

Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

Author information

1
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
2
Department of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
3
Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
4
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
5
International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
6
Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois.
7
Han Kang Ltda, Santiago, Chile.

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.

KEYWORDS:

HCC; TIPRL; TRAIL resistance; Taraxacum officinale F.H. Wigg; apoptosis

PMID:
25647515
DOI:
10.1002/mc.22288
[Indexed for MEDLINE]

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