Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.
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.
['Yoon|Ji-Yong|JY|', 'Cho|Hyun-Soo|HS|', 'Lee|Jeong-Ju|JJ|', 'Lee|Hyo-Jung|HJ|', 'Jun|Soo Young|SY|', 'Lee|Jae-Hye|JH|', 'Song|Hyuk-Hwan|HH|', 'Choi|SangHo|S|', 'Saloura|Vassiliki|V|', 'Park|Choon Gil|CG|', 'Kim|Cheol-Hee|CH|', 'Kim|Nam-Soon|NS|']
D000972:Antineoplastic Agents, Phytogenic D017209:Apoptosis D006528:Carcinoma, Hepatocellular D045744:Cell Line, Tumor D019008:Drug Resistance, Neoplasm D004789:Enzyme Activation D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D048031:JNK Mitogen-Activated Protein Kinases D008099:Liver D008113:Liver Neoplasms D048688:MAP Kinase Kinase 7 D060066:Protein Interaction Maps D015398:Signal Transduction D053221:TNF-Related Apoptosis-Inducing Ligand D031205:Taraxacum
Taraxacum officinale F.H. Wigg apoptosis TRAIL resistance TIPRL HCC