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

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

MeSH: Anthocyanins/administration & dosage ; Anthocyanins/pharmacology* ; Antineoplastic Combined Chemotherapy Protocols/pharmacology* ; Apoptosis/drug effects ; Caspases/metabolism ; Cell Line, Tumor ; Drug Synergism ; Histone Deacetylases/metabolism* ; Humans ; Male ; Prostatic Neoplasms/drug therapy* ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis* ; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism ; TNF-Related Apoptosis-Inducing Ligand/administration & dosage ; TNF-Related Apoptosis-Inducing Ligand/pharmacology* ; Transfection

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.