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Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL‐induced apoptosis in Huh7 cells
Author(s) -
Yoon JiYong,
Cho HyunSoo,
Lee JeongJu,
Lee HyoJung,
Jun Soo Young,
Lee JaeHye,
Song HyukHwan,
Choi SangHo,
Saloura Vassiliki,
Park Choon Gil,
Kim CheolHee,
Kim NamSoon
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22288
Subject(s) - apoptosis , gene knockdown , biology , cancer cell , kinase , phosphorylation , cancer research , cancer , pharmacology , microbiology and biotechnology , biochemistry , genetics
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.