Oncotarget

Research Papers:

Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage

Hyeonseok Ko, Mi-Hyeon Jeong, Hyelin Jeon, Gi-Jun Sung, Youngsin So, InKi Kim, JaeKyoung Son, Sang-wook Lee, Ho-Geun Yoon and Kyung-Chul Choi _

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Oncotarget. 2015; 6:9970-9984. https://doi.org/10.18632/oncotarget.3667

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Abstract

Hyeonseok Ko5,*, Mi-Hyeon Jeong1,4,* , Hyelin Jeon1, Gi-Jun Sung1, Youngsin So1, InKi Kim3, JaeKyoung Son1, Sang-wook Lee2, Ho-Geun Yoon4, Kyung-Chul Choi1

1 Department of Biomedical Sciences and Department of Pharmacology, University of Ulsan College of Medicine, Seoul, Korea

2 Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

3 Asan Institute for Medical Research, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea

4 Department of Biochemistry and Molecular Biology, Brain Korea PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea

5 Laboratory of Molecular Oncology, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Dankook University, Seoul, South Korea

* These authors are co-first authors and contributed equally to this work

Correspondence to:

Kyung-Chul Choi, email:

Ho-Geun Yoon, email:

Keywords: delphinidin, TRAIL, apoptosis, HDAC3, prostate cancer

Received: November 13, 2014 Accepted: February 12, 2015 Published: March 26, 2015

Abstract

TRAIL can induce apoptosis in some cancer cells and is an immune effector in the surveillance and elimination of developing tumors. Yes, some cancers are resistant to TRAIL. Delphinidin, a polyphenolic compound contained in brightly colored fruits and vegetables, has anti-inflammatory, anti-oxidant, and anti-tumorigenic activities. Here we showed that delphinidin sensitized TRAIL-resistant human prostate cancer cells to undergo apoptosis. Cells treated with delphinidin and TRAIL activated the extrinsic and intrinsic pathways of caspase activation. TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3). In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage. Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.


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