Geraniol suppresses prostate cancer growth through down-regulation of E2F8.
Geraniol, an acyclic dietary monoterpene, has been found to suppress cancer survival and growth. However, the molecular mechanism underlying the antitumor action of geraniol has not been investigated at the genome-wide level. In this study, we analyzed the microarray data obtained from geraniol-treated prostate cancer cells. Geraniol potently altered a gene expression profile and primarily down-regulated cell cycle-related gene signatures, compared to linalool, another structurally similar monoterpene that induces no apparent phenotypic changes. Master regulator analysis using the prostate cancer-specific regulatory interactome identified that the transcription factor E2F8 as a specific target molecule regulates geraniol-specific cell cycle signatures. Subsequent experiments confirmed that geraniol down-regulated E2F8 expression and the knockdown of E2F8 was sufficient to suppress cell growth by inducing G2/M arrest. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. Therefore, our study provides insight into the role of E2F8 in prostate cancer biology and therapeutics.
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah, 84112 5650.
Sanghoon
S
Lee
Office of Clinical Research Information, Asan Medical Center, Seoul, 05535, Korea.
Yu Rang
YR
Park
Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea.
Su-Hwa
SH
Kim
Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea.
Eun-Jung
EJ
Park
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 05535, Korea.
Min Ji
MJ
Kang
Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea.|Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, Korea.
Insuk
I
So
Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea. jnchun@gmail.com.|Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, Korea. jnchun@gmail.com.
Jung Nyeo
JN
Chun
Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea. jhjeon2@snu.ac.kr.|Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, Korea. jhjeon2@snu.ac.kr.
Ju-Hong
JH
Jeon
D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D013729:Terpenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents; C504723:E2F8 protein, human; D039821:Monoterpenes; D012097:Repressor Proteins; D013729:Terpenes; C018584:linalool; C007836:geraniol
Bioinformatics; E2F8; cell cycle control; clustering analysis; geraniol; master regulator analysis; prostate cancer
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