beta-ionone and Adenocarcinoma

β-ionone is a terminal cyclic analog of beta-carotenoids widely found in plants. In recent years, accumulating evidence has shown that β-ionone exerts antitumor effects on various malignant tumors. However, limited studies have revealed the role of β-ionone in regulating the epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells. This study aimed to investigate the effect of β-ionone on the EMT process of PCa, focusing on Wnt/β-catenin signaling pathway.. After exposure to β-ionone, cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the Brdu proliferation assay. The Transwell and wounding healing were used to investigate the migration and invasion abilities of PCa cells. Expression of proteins involved in the EMT process (E-cadherin, N-cadherin, vimentin) and proteins in the Wnt/β-catenin pathway (β-catenin, GSK3-β, and p-GSK3-β) were explored by western blotting. The effects of β-ionone on β-catenin degradation were explored by cycloheximide tracking assay and. The migration, invasion, and EMT process of PCa Human PC-3 prostate adenocarcinoma cells (PC3) and Human 22RV1 prostate adenocarcinoma cells (22RV1) cells were significantly inhibited after β-ionone treatment. In addition, β-ionone also inhibited the growth and EMT process of subcutaneous xenograft tumors in nude mice. The study also found that β-catenin, which promotes EMT, was downregulated after β-ionone treatment. Further mechanistic studies revealed that β-ionone inhibited the Wnt/β-catenin pathway by accelerating the ubiquitination and degradation of β-catenin in PCa, thus inhibiting the downstream migration, invasion, and EMT processes.. These findings demonstrate that β-ionone may be a potential natural compound targeting the Wnt/β-catenin pathway for the treatment of PCa.

Topics: Adenocarcinoma; Animals; beta Catenin; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Glycogen Synthase Kinase 3; Humans; Male; Mice; Mice, Nude; Prostate; Prostatic Neoplasms; Wnt Signaling Pathway

β-Ionone is an end ring analog of β-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of β-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. We found that the β-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). β-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells. These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins. These results demonstrate potent ability of β-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation.

Topics: Adenocarcinoma; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; DNA; Dose-Response Relationship, Drug; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; G1 Phase Cell Cycle Checkpoints; Humans; MAP Kinase Signaling System; Norisoprenoids; Resting Phase, Cell Cycle; Stomach Neoplasms

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is the rate-limiting activity in the mevalonate pathway that provides essential intermediates for posttranslational modification of growth-associated proteins. Assorted dietary isoprenoids found in plant foods suppress HMG CoA reductase and have cancer chemopreventive activity. β-Ionone, a cyclic sesquiterpene and an end-ring analog of β-carotene, induced concentration-dependent inhibition of the proliferation of human DU145 (IC50 = 210 μmol/L) and LNCaP (IC50 = 130 μmol/L) prostate carcinoma cells and PC-3 prostate adenocarcinoma cells (IC50 = 130 μmol/L). Concomitantly, β-ionone-induced apoptosis and cell cycle arrest at the G1 phase in DU145 and PC-3 cells were shown by fluorescence microscopy, flow cytometry, and TUNEL reaction, and downregulation of cyclin-dependent kinase 4 (Cdk4) and cyclin D1 proteins. Growth suppression was accompanied by β-ionone-induced downregulation of reductase protein. A blend of β-ionone (150 μmol/L) and trans, trans-farnesol (25 μmol/L), an acyclic sesquiterpene that putatively initiates the degradation of reductase, suppressed the net growth of DU145 cells by 73%, an impact exceeding the sum of those of β-ionone (36%) and farnesol (22%), suggesting a synergistic effect. β-ionone, individually or in combination with other HMG CoA reductase suppressors, may have potential in prostate cancer chemoprevention and/or therapy.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma; Cell Cycle Checkpoints; Cell Line, Tumor; Dose-Response Relationship, Drug; Farnesol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inhibitory Concentration 50; Male; Norisoprenoids; Prostatic Neoplasms

β-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of β-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K)-AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that β-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. β-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after β-ionone treatments in a time- and dose-dependent manner (P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by β-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which β-ionone to induce apoptosis initiation in SGC-7901 cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Nucleus Shape; Cell Survival; Dose-Response Relationship, Drug; Humans; Norisoprenoids; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Stomach Neoplasms; Time Factors

In order to determine the inhibitory effects and apoptosis of beta-ionone in human gastric carcinoma SGC-7901 cell line and its possible mechanism.. The assays of the curves of cell proliferation, cell mitosis, Hoechst 33258 dye stained, emission electronic microscope, and western blotting were employed.. Beta-ionone could inhibit the growth and cell mitosis in SGC-7901 cells. The EC50 value was (174.93 +/- 12.79) micromol/L. Morphology of apoptosis was observed by Hoechst 33258 dye stained and emission electronic microscope. The fragmentation of activated caspase-3 was induced and expression of Erkl/2 protein was decreased in SGC-7901 cells treated with different levels of beta-ionone.. Thus beta-ionone could induce apoptosis in SGC-7901 cells and exactly mechanism needed further to be studied.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Cell Line, Tumor; Humans; Mitogen-Activated Protein Kinase 3; Norisoprenoids; Stomach Neoplasms

To determine the effect of beta-ionone on the potential metastasis of human gastric adenocarcinoma cell line SGC-7901 and the underlying mechanism.. Using curve of cellular growth, Zymograms, and RT-PCR assays, we analyzed the growth rate, the activities of two types IV collagenase of Matrix met alloproteinase 9 (MMP-9) and MMP-2 and the expression of nm23-H1 gene, tissue inhibitor of met alloproteinase 1 (TIMP-1) and TIMP-2 in SGC-7901 cells which were treated with progressively increasing concentrations (25, 50, 100 and 200 micromol/L) of beta-ionone for 24 h and 48 h.. The growth of SGC-7901 cells was inhibited by beta-ionone. Eight days after treatment with different concentrations of beta-ionone, as mentioned above, the inhibition rates were 25.93%, 28.21%, 74.36% and 90.11%, respectively compared to the negative control. The estimated IC50 value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L; beta-ionone did not show any effect on the activities of MMP-9 and MMP-2 in SGC-7901 cells. However, the expression of nm23-H1, TIMP-1 and TIMP-2 mRNA transcripts gradually increased in response to beta-ionone in a dose-dependent manner.. beta-ionone can inhibit the growth and proliferation of SGC-7901 cells. It may show some effects on the potential metastasis of SGC-7901 cells indicates by its upregulation of nm23-H1, TIMP-1 and TIMP-2 expression. However, beta-ionone may have no effect on the activities of type IV collagenase in SGC-7901 cells. The mechanism by which beta-ionone inhibits the potential metastasis of SGC-7901 cells needs to be studied further.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Humans; Neoplasm Metastasis; NM23 Nucleoside Diphosphate Kinases; Norisoprenoids; RNA, Messenger; Stomach Neoplasms; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

To observe the effect of beta-ionone on the proliferation of human gastric adenocarcinoma cell line SGC-7901 and the inhibition of metalloproteinase.. Using growth inhibition, Zymograms assays and reverse transcription-polymerase-chain reaction (RT-PCR), we examined cell growth rates, activities of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9), and expression of metalloproteinases-1 (TIMP-1) and -2 (TIMP-2) in SGC-7901 cells after the treatment with beta-ionone for 24 h and 48 h, respectively.. beta-ionone had an inhibitory effect on the growth of SGC-7901 cells. Eight days after the treatment with beta-ionone at concentrations of 25, 50, 100 and 200 micromol/L, the inhibition rates were 25.9%, 28.2%, 74.4% and 90.1%, respectively. The IC50 value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L. The effects of beta-ionone on MMP-2 and MMP-9 activities in SGC-7901 cells were not observed. However, the levels of TIMP-1 and TIMP-2 transcripts were elevated in cells treated with beta-ionone in a dose-dependent manner.. beta-ionone can inhibit the proliferation of SGC-7901 cells, upregulate the expression of TIMP-1 and TIMP-2 expression, and may influence metastasis of cancer.

Topics: Adenocarcinoma; Cell Division; Cell Line, Tumor; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Norisoprenoids; RNA, Messenger; Stomach Neoplasms; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Up-Regulation

To investigate the effect of beta-ionone on the growth and apoptosis of gastric adenocarcinoma cell line SGC-7901.. Using MTT, fluorescence dye (Hoechst-33258), transmission electron microscopy and the TUNEL assay, we examined growth and apoptosis of SGC-7901 cells treated with beta-ionone at various concentrations (i.e. 25, 50, 100 and 200 micromol/L) for 24 h, 48 h.. The growth of SGC-7901 cells was inhibited by beta-ionone. Seven days after treatment with beta-ionone at four concentrations, the inhibition rates were 12.04%, 30.59%, 78.25% and 94.15%, respectively. The IC(50) value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L. The apoptotic morphology was demonstrated in SGC-7901 cells treated with beta-ionone by Hoechst-33258 staining and electron microscopy. Apoptosis was also shown in beta-ionone-treated SGC-7901 cells by the TUNEL assay.. beta-ionone can inhibit cell proliferation and induce apoptosis of SGC-7901 cells. However, the mechanism needs to be further investigated.

Topics: Adenocarcinoma; Apoptosis; Cell Line, Tumor; Humans; Norisoprenoids; Stomach Neoplasms

To investigate the effect of cell proliferation induced by beta-ionone.. Human mammary cancer cells (MCF-7) were treated with various beta-ionone concentrations (25, 50, 100 and 200 mumol/L), with a negative control. Methods such as curve of cell growth, cellular mitosis, the cell clone formatting and DNA synthesis were employed.. beta-ionone inhibited the cell proliferation, cellular mitosis, the cell clone formatting and DNA synthesis. The inhibitory frequency (IF) showed a dose-dependent response as the concentrations of beta-ionone increased. Its IC50 value was 104 mumol/L for MCF-7 cells. The inhibitory frequency (IF) from cellular mitosis of MCF-7 treated by beta-ionone were - 12.88% - 68.67% at 24 h and 20.79% - 87.79% at 48 h, from the cell clone formatting of MCF-7 treated by beta-ionone, were - 14.11% - 65.18% at 24 h and 6.58% - 72.48% at 48 h, from DNA synthesis, 16.75% - 65.33% at 24 h and 35.10% - 81.89% at 48 h.. beta-ionone could inhibit the cell growth of MCF-7 cells and the mechanisms needs to be further studied.

Topics: Adenocarcinoma; Antineoplastic Agents; Breast Neoplasms; Cell Division; DNA, Neoplasm; Female; Humans; Norisoprenoids; Tumor Cells, Cultured