title: Emodin inhibits the proliferation of PC3 prostate cancer cells in vitro via the Notch signaling pathway.
abstract: The aim of the present study was to examine the anticarcinogenic effects of emodin on the Notch signaling pathway and vascular endothelial growth factor (VEGF) in the PC3 androgen-independent prostate cancer cell line in vitro. The cell viability was assessed using an 3‑(4,5)‑dimethylthiahiazo(‑z‑y1)‑3,5‑di‑phenytetrazolium bromide assay. Cell apoptosis and cell cycle were detected using flow cytometry. Morphological alterations were observed using transmission electron microscopy. The mRNA and protein expression levels of Notch1, Jagged1, VEGF and bFGF were detected using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Laser scanning confocal microscope (LSCM) immunofluorescence analysis was performed to detect the levels of expression and the sub‑cellular localization of the Notch1 receptor protein. Growth of the PC3 cells was inhibited by emodin. Flow cytometry demonstrated that emodin induced apoptosis in the PC3 cells and arrested the cell cycle of the PC3 cells at the G2/M phase. The mRNA and protein expression of Notch1 in the PC3 cells was markedly increased, whereas the mRNA and protein expression levels of Jagged1, VEGF and bFGF were significantly decreased following exposure to emodin for 24 h. The LSCM assay revealed that the Notch1 was not only localized in the membrane and cytoplasm, but was also present in the nucleolus of the PC3 cells, and the expression of Notch1 in the nuclei gradually increased following treatment with emodin. These results demonstrated that emodin suppressed the growth of androgen‑independent prostate cancer cell lines and induced apoptosis and cell cycle arrest. The Notch signaling pathway was activated in the PC3 cells following exposure to emodin, which suggested that the Notch signaling pathway is involved in the prostate tumor‑suppressing mechanisms of emodin, the activation of which may depend on CBF1 protein in the nucleus by classic pathways. The antitumor function of emodin, attributed to the Notch signaling pathway, induced the downregulation of VEGF by suppressing tumorigenesis and angiogenesis, which indicated a novel mechanism underlying the emodin-mediated anti-prostate cancer effect.
authors.affiliation: Division of Urology, The First People's Hospital of Hangzhou, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Deng
authors.affiliation: Division of Urology, The First People's Hospital of Hangzhou, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ju
authors.affiliation: Division of Urology, The First People's Hospital of Hangzhou, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Division of Urology, The First People's Hospital of Hangzhou, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Division of Urology, The First People's Hospital of Hangzhou, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004642:Emodin / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D021381:Protein Transport; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004642:Emodin