cyclin-d1 and ferulic-acid

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carcinogens; Cell Proliferation; Cell Transformation, Neoplastic; Coumaric Acids; Cricetinae; Cyclin D1; Immunoenzyme Techniques; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Neoplasms, Experimental; Proliferating Cell Nuclear Antigen; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Angelicae Sinensis is a well known and commonly used traditional Chinese herbal medicine with many therapeutic effects such as neuroprotection, the promotion of hematopoiesis and the treatment of tumors.. Ferulic acid (FA) is the main active component in Angelicae Sinensis. Previous research has demonstrated that Angelicae Sinensis is able to induce angiogenesis in vivo. This study investigated the effects of FA on the proliferation of a human umbilical vein endothelial cell line (ECV304) with regard to the modulation of endothelial cells, which is a key step of angiogenesis.. ECV304 cells were incubated with FA at different dosages (0.1 μg/mL, 1 μg/mL and 10 μg/mL). A series of assays was used to detect the effects of FA on: (i) cell proliferation; (ii) DNA synthesis; (iii) cell-cycle distribution; and (iv) mRNA expression of cyclin D1 and vascular endothelial growth factor (VEGF). These were assessed using the Cell Counting Kit-8 (CCK-8), bromodeoxyuridine-enzyme-linked immunosorbent assay (BrdU-ELISA), flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), respectively.. The results showed that FA at a range of concentrations from 0.1 μg/mL to 10 μg/mL could markedly improve cell proliferation and DNA synthesis in a dose-dependent manner. Flow cytometry showed a significant decrease in the percentage of cells in the G(0)/G(1) phase and a significant increase in the percentage of cells in the S phase. Furthermore, we found that FA enhanced cyclin D1 and VEGF mRNA expression in ECV304 cells.. FA was able to promote ECV304 cells proliferation in vitro. This effect might be observed through the modulation of cyclin D1 and VEGF.

Topics: Angiogenesis Modulating Agents; Cell Culture Techniques; Cell Cycle; Cell Line; Cell Proliferation; Coumaric Acids; Cyclin D1; DNA; Dose-Response Relationship, Drug; Endothelial Cells; Humans; Up-Regulation; Vascular Endothelial Growth Factor A

The molecular mechanisms underlying the mitogenic effect of ferulic acid (FA), an active compound derived from Angelica sinensis, have never been elucidated. It was the aim of this study to investigate the proliferative effect of FA on human breast cancer cell lines and to elucidate its modulation mechanism on HER2 expression in MCF7 line.. By using MCF7 (oestrogen receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER-, HER2-low) and SKBR3 (ER-, HER2-high) human breast cancer cell lines as in vitro models, the mitogenic effects of FA were assessed by trypan blue dye exclusion assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2 gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR analysis.. Ferulic acid ER-dependently stimulated cell proliferation on MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha; ERalpha) transcription were markedly up-regulated by FA treatment. Besides, HER2 signalling and its downstream molecules such as AKT and ERK1/2 were involved in FA-modulated ERalpha and cyclin D1 synthesis. Addition of anti-HER2 antibody, trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated a positive feedback control for the action of HER2 in this setting. The fact that the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that trastuzumab down-regulated ERalpha gene expression, suggested a cross-talk between ERalpha and HER2 signalling on MCF7 cells.. The authors' conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression.

Topics: Antibodies, Neoplasm; Breast Neoplasms; Cell Line, Tumor; Coumaric Acids; Cyclin D1; Dose-Response Relationship, Drug; Estrogen Receptor alpha; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Mitogen-Activated Protein Kinase 1; Mitogens; Mitosis; Proto-Oncogene Proteins c-akt; Signal Transduction; Up-Regulation

The aim of this study was to determine the effects of ferulic acid on the proliferation and molecular mechanism in cultured vascular smooth muscle cell (VSMC) induced by angiotensin II. It was shown that ferulic acid significantly inhibited angiotensin II-induced VSMC proliferation in a dose-dependent manner. Western blotting analyses suggest that the antiproliferative effect of ferulic acid was involved in the mitogen-activated protein kinases (MAPKs) pathway. While no effect on p38, ferulic acid markedly inactivated the extracellular signal-regulated kinases (ERK1/2) and c-Jun N-terminal kinases (JNK), indicating that the inhibition of ferulic acid on VSMC proliferation was associated with ERK1/2 and JNK rather than p38 pathway. On the expression of cell cycle regulatory proteins, ferulic acid elevated the protein content of p21(waf1/cip1), decreased expression of cyclin D1 and inhibited phosphorylation of retinoblastoma protein, suggesting that ferulic acid inhibited VSMC proliferation by regulating the cell progression from G1 to S phase. The inactivation of MAPKs and modulation of cell cycle proteins of ferulic acid may be of importance in preventing cardiovascular disease.

Topics: Angiotensin II; Animals; Blotting, Western; Cell Cycle Proteins; Cell Proliferation; Cells, Cultured; Coumaric Acids; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Dose-Response Relationship, Drug; Enzyme Activation; Male; Mitogen-Activated Protein Kinases; Muscle, Smooth, Vascular; Rats; Rats, Wistar; Retinoblastoma Protein

The aim of this study was to determine the antiproliferative mechanism of ferulic acid (FA) on serum induced ECV304 cell, a human umbilical vein endothelial line. The results suggest that FA significantly suppressed ECV304 cells proliferation and blocked the cell cycle in G0/G1 phase. Treatment of the cells with FA increased nitric oxide (NO) production and inactivated the extracellular signal-regulated kinase (EERK1/2), and the NO donor, sodium nitroprusside, inhibited both ECV304 cells proliferation and phosphorylation of ERK1/2. However, the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester, caused ECV304 cells proliferation. PD 98059, the inhibitor of ERK1/2, had no effect on the NO production. These results indicate that NO suppressed ECV304 cells proliferation through down-regulating ERK1/2 pathway. Moreover, the inhibition of cell cycle progression was associated with the decrement of cyclin D1 expression and phosphorylation of retinoblastoma protein (pRb) by increment of p21 level. The findings not only present the first evidence that FA is a potent inhibitor on ECV304 cells proliferation, but also reveal the potential signaling molecules involved in its action.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Cycle; Cell Proliferation; Cells, Cultured; Coumaric Acids; Cyclin D1; Down-Regulation; Endothelium, Vascular; Enzyme Activation; Humans; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Nitric Oxide; Nitrites; Phosphorylation; Retinoblastoma Protein; Signal Transduction; Umbilical Cord