title: Delphinidin induces apoptosis via cleaved HDAC3-mediated p53 acetylation and oligomerization in prostate cancer cells.
abstract: Delphinidin is a major anthocyanidin compound found in various fruits. It has anti-inflammatory, anti-oxidant, and various other biological activities. In this study, we identified the epigenetic modulators that mediate the apoptotic effect of delphinidin in human prostate cancer cells. We found that treatment of LNCaP cells (a p53 wild-type, human prostate cancer cell line) with delphinidin increased caspase-3, -7, and -8 activity, whereas it decreased histone deacetylase activity. Among class I HDACs, the activity of HDAC3 was specifically inhibited by delphinidin. Moreover, the induction of apoptosis by delphinidin was dependent on caspase-mediated cleavage of HDAC3, which results in the acetylation and stabilization of p53. We also observed that delphinidin potently upregulated pro-apoptotic genes that are positively regulated by p53, and downregulated various anti-apoptotic genes. Taken together, these results show that delphinidin induces p53-mediated apoptosis by suppressing HDAC activity and activating p53 acetylation in human prostate cancer LNCaP cells. Therefore, delphinidin may be useful in the prevention of prostate cancer.
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.|Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Mi-Hyeon
authors.initials: MH
authors.lastname: Jeong
authors.affiliation: Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.|Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Hyelin
authors.initials: H
authors.lastname: Jeon
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.|Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Gi-Jun
authors.initials: GJ
authors.lastname: Sung
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Chonnam National University, Gwangju, South Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Jun
authors.affiliation: Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do, South Korea.
authors.forename: Yoo-Hyun
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Medical Nutrition, Kyung Hee University, Yongin-si, Kyunggi-do, South Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.|Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.|Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
mesh_terms: D000107:Acetylation; D000872:Anthocyanins / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D000872:Anthocyanins; D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D006655:Histone Deacetylases; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D000099186:Histone Deacetylase 3; C495901:TP53 protein, human; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C505530:CASP8 protein, human; C017185:delphinidin
keywords: HDAC3; acetylation; apoptosis; delphinidin; p53