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Objectives This study aimed to clarify the superior beneficial effects of icariin on atherosclerosis, as well as to explore the possible underlying mechanisms for its effect via the modulation of protein kinase C ßI. Methods Lipid profiles were determined while dissected aortas were prepared of ApoE-/- mice. The expression of protein kinase C ßI and phosphorylation of protein kinase C ßI were determined by immunohistochemistry analysis. Human vascular smooth muscle cells were subjected to ox-LDL stimulation. MTS assay was conducted to detect cell proliferation. A transwell migration assay was performed to evaluate migration capacity. Flow cytometric analysis was used to determine cell cycle progression. Quantitative real-time PCR and western blot were performed to assess gene expression. Results Icariin significantly alleviated atherogenesis, as well as protein levels of protein kinase C ßI and phosphorylated protein kinase C ßI in the aorta. Icariin effectively suppressed cell proliferation and migration. protein kinase C ßI, cyclin D1 and matrix metalloproteinase-9 were modulated in response to treatment with icariin. Protein kinase C activator reversed the protective effect of icariin on human vascular smooth muscle cells against ox-low-density lipoprotein, protein kinase C ß inhibitor augmented the inhibitory effect of icariin. Conclusions Our findings highlight the probable application of icariin in atherosclerotic therapy and reveal that protein kinase C ßI acts as a crucial regulator in the anti-atherosclerotic action of icariin. [ABSTRACT FROM AUTHOR]

Objectives: Regorafenib is an oral multi-kinase inhibitor approved for various metastatic/advanced cancers, and has been investigated in clinical trials in many other tumour entities. The purpose of this study was to evaluate the therapeutic potential of regorafenib for nasopharyngeal carcinoma (NPC). Methods: Cellular proliferation, survival, apoptosis and colony formation assays were performed and combination index was determined. NPC xenograft tumour models were established. In vitro and In vivo angiogenesis assays were performed. Key findings: Regorafenib is effective against a panel of NPC cell lines regardless of cellular origin and genetic profiling while sparing normal nasal epithelial cells. The predominant inhibitory effects of regorafenib in NPC are anchorage-dependent and anchorage-independent growth rather than survival. Apart from tumour cells, regorafenib potently inhibits angiogenesis. Mechanistically, regorafenib inhibits multiple oncogenic pathways including Raf/Erk/Mek and PI3K/Akt/mTOR. Regorafenib decreases Bcl-2 but not Mcl-1 level in NPC cells. The in vitro observations are evident in in vivo NPC xenograft mouse model. The combination of Mcl-1 inhibitor with regorafenib is synergistic in inhibiting NPC growth without causing systemic toxicity in mice. Conclusions: Our findings also support further clinical investigation of regorafenib and Mcl-1 inhibitor for NPC treatment. [ABSTRACT FROM AUTHOR]

Objectives Ovarian cancer is a lethal gynecological malignancy. Long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was reported to have a critical role in cancer advancement. The ANRIL-mediated oncogenic underlying molecular mechanisms are not fully understood in ovarian cancer. We aimed to study ANRIL silencing effects on the proliferation and apoptosis of OVCAR-3 cells. Methods The ANRIL was Knockdown by transfection of OVCAR-3 cells with si-RNA against ANRIL. MTT assay and cell death ELISA kit were used to evaluate cellular proliferation and apoptosis. The expression levels of ANRIL, pro-and anti-apoptotic genes were assessed using q-RT-PCR. Western blotting was used to assess Wnt/ß-catenin signalling pathway. Key findings ANRIL down-regulating in OVCAR-3 cell lines resulted in significant inhibition of cellular proliferation, apoptosis induction, as well as suppression of cellular invasion. Besides, knockdown of ANRIL led to pro-apoptotic genes up-regulation, Bad and Bax and anti-apoptotic genes down-regulation, Bid and Bcl-2. More importantly, we observed that ANRIL inhibition suppressed the vital components expression of the Wnt/ß-catenin cascade. Conclusion Our findings showed that down-regulation of lncRNA ANRIL resulted in the effective suppression of OVCAR-3 cell proliferation and invasion and induction of apoptosis by preventing Wnt/ß-catenin signal transduction. [ABSTRACT FROM AUTHOR]

Objectives The aim of the current study was to identify the long noncoding RNAs (lncRNAs) ANRIL function and molecular pathways underlying hepatocellular carcinoma progression. Methods ANRIL knockdown with specific siRNA, and transfected into HepG2 cells according to the protocol of Lipofectamine 2000. Cell proliferation, apoptosis, migration and metastasis were assessed with MTT assay, flow cytometry and wound healing assay, respectively. Moreover, the expression level of ANRIL, apoptosis-related genes, and the Wnt pathway-associated genes were assessed by real time-PCR and Western blot assay. Key findings Knocking down of ANRIL led to alleviated cell growth and increased cell apoptosis of HepG2 cells through markedly increased expression levels of Bax and Bad. In contrast, dramatically diminished the expressions of anti-apoptotic factors including Bid and Bcl-2 in comparison to the scrambled control group (si-NC). Furthermore, ANRIL silencing resulted in an inactivated Wnt/β-catenin pathway by suppressing key genes associated with this pathway. Conclusions Taken together, these findings imply new insights into the regulatory network of the Wnt pathway through lncRNA ANRIL that indicate ANRIL may be a therapeutic factor potential for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Objectives Accumulated evidence demonstrates that propofol has antitumour roles in various cancers. However, the role of propofol in osteosarcoma is still unclear. Therefore, we aim to determine the role of propofol on osteosarcoma and further explore its potential mechanism. Methods Cell proliferation, migration and invasion of osteosarcoma were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing and transwell assay, respectively. The interaction between FoxO1 and TUSC7 was determined using luciferase reporter assay and chromatin immunoprecipitation. Results Propofol treatment significantly decreased cell proliferation, migration and invasion in U2OS cells. Propofol promoted TUSC7 expression by enhancing transcriptional factor FOXO1 that leads to inactivation of AKT/GSK3ß signalling resulting in the suppression of cell proliferation, migration and invasion. Conclusions Propofol suppresses cell proliferation, migration and invasion of osteosarcoma cells through FOXO1/TUSC7 axis by regulating AKT/GSK3ß signalling. [ABSTRACT FROM AUTHOR]

Objectives: To examine the antiproliferative effect of a rationally designed, novel noscapine analogue, 9‐((perfluorophenyl)methylene) aminonoscapine, '9‐PAN') on MDA‐MB‐231 breast cancer cell line, and to elucidate the underlying mechanism of action. Methods: The rationally designed Schiff base‐containing compound, 9‐PAN, was characterized using IR, NMR and mass spectra analysis. The effect of the compound on cell viability was studied using an MTT assay. Cell cycle and cell death analyses were performed using flow cytometry. Binding interactions of 9‐PAN with tubulin were studied using spectrofluorometry. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were investigated using the probes, DCFDA and rhodamine‐123, respectively. Immunofluorescence imaging was used to visualize cellular microtubules. Key findings: 9‐PAN inhibited cell proliferation (IC50 of 20 ± 0.3 µm) and colony formation (IC50, 6.2 ± 0.3 µm) by arresting the cells at G2/M phase of the cell cycle. It bound to tubulin in a concentration‐dependent manner without considerably altering the tertiary conformation of the protein or the polymer mass of the microtubules in vitro. The noscapinoid substantially damaged cellular microtubule network and induced cell death, facilitated by elevated levels of ROS. Conclusions: 9‐PAN exerts its antiproliferative effect by targeting tubulin and elevating ROS level in the cells. [ABSTRACT FROM AUTHOR]

Objectives Vascular smooth muscle cell (VSMC) migration and proliferation at sites of vascular injury are both critical steps in the development of intimal hyperplasia (IH). Local delivery of nitric oxide (NO) largely prevents these events. Among the NO donors, tetraazamacrocyclic nitrosyl complexes, such as trans-[Ru(NO)Cl(cyclam)](PF6)2 (cyclamNO), gained attention for their features, which include the possibility of being embedded in solid matrices, and ability to participate in a nitrite/NO catalytic conversion cycle. Methods Methods used to evaluate cyclamNO activity: safety margin by NR and MTT; cell proliferation by 3H-thymidine incorporation and proliferating cell nuclear antigen (PCNA) expression; antimigratory properties by transwell and wound healing; prevention of cell phenotypic switching under platelet-derived growth factor type BB (PDGF-BB) stimuli by analysis of alpha smooth muscle actin (α-SMA) expression. Key findings Cell proliferation and migration induced by PDGF-BB were significantly inhibited by cyclamNO. The ~60% reduction on expression of contractile protein α-SMA induced by PDGF-BB revealed VSMC phenotypic switching which is significantly prevented by cyclamNO. Compared to the NO donor sodium nitroprusside, cyclamNO showed to be significantly less cytotoxic. Conclusions With great potential to maintain VSMC functionality and prevent IH-associated events, cyclamNO might be a promissory drug for several applications in cardiovascular medicine, as in stents. [ABSTRACT FROM AUTHOR]

Objective Red propolis, an exclusive variety of propolis found in the northeast of Brazil has shown to present antitumour activity, among several other biological properties. This article aimed to help to evaluate the underlying molecular mechanisms of the potential anticancer effects of red propolis on tumour, Hep-2, and non-tumour cells, Hek-293. Methods Differentially expressed proteins in human cell lines were identified through label-free quantitative MS-based proteomic platform, and cells were stained with Giemsa to show morphological changes. Key findings A total of 1336 and 773 proteins were identified for Hep-2 and Hek-293, respectively. Among the proteins here identified, 16 were regulated in the Hep-2 cell line and 04 proteins in the Hek-293 line. Over a total of 2000 proteins were identified under MS analysis, and approximately 1% presented differential expression patterns. The GO annotation using Protein Analysis THrough Evolutionary Relationships classification system revealed predominant molecular function of catalytic activity, and among the biological processes, the most prominent was associated to cell metabolism. Conclusion The proteomic profile here presented should help to elucidate further molecular mechanisms involved in inhibition of cancer cell proliferation by red propolis, which remain unclear to date. [ABSTRACT FROM AUTHOR]

Objectives Our study aimed to evaluate the effect of cordycepin on human lung cancer cell lines A549 and NCI-H460. Methods Human lung cancer A549 cells and NCI-H460 cells were treated with different concentrations of cordycepin for different times. Cells incubated without cordycepin were defined as a control. The cell proliferation, migration and apoptosis were, respectively, determined by MTT assay, transwell migration assay and flow cytometry. Additionally, the expression levels of related proteins associated with cell cycle, epithelial-mesenchymal transition ( EMT) and apoptosis were examined. Key findings The survival rate of A549 cells and NCI-H460 cells treated with cordycepin significantly decreased compared with untreated cells in a concentration-dependent manner, while the apoptosis rate increased. The migration number of cells treated with cordycepin significantly decreased as the increase in concentration. qRT- PCR and Western blot analysis showed that the aberrant expression of related molecules associated with cell cycle, m igration and apoptosis was observed in the lung cancer cells, such as cyclin B, cyclin E, MMP-9, caspase-3 and Bcl-2. Conclusions Cordycepin may exert inhibitory effects on the development of human lung cancer via inhibiting cell proliferation, suppressing m igration and inducing apoptosis, suggesting that cordycepin may have therapeutic potential for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Objectives Sorafenib is a first multi-kinase inhibitor and one of the most widely used small-molecule oral-targeted drugs. It has been widely used for the treatment of patients with advanced renal cell carcinoma and hepatocellular carcinoma. However, some common adverse effects of sorafenib may impact quality of life. In this study, we evaluated the inhibitory effect on the growth of hepatocellular carcinoma cell line ( HepG2) and suppression on angiogenesis of 1118-20, a newly synthesized indazole diarylurea compound. Methods We evaluated the activity of 1118-20 against HepG2 cells growth and tumour angiogenesis of human umbilical vascular endothelial cell line ( HUVECs) with sorafenib as a positive control. Key findings The cytotoxic efficacy of 1118-20 was higher in HepG2 cells than human normal liver cell line ( HL-7702). 1118-20 significantly suppressed the proliferation of HepG2 cells by apoptosis induction via Bcl-2 family-mediated mitochondria pathway and inhibition on Wnt/β-catenin signalling pathway. 1118-20 effectively blunt the motility and migration, and inhibited the formation of capillary tube of HUVECs through suppression of angiogenic factors expression. Moreover, the results indicated that 1118-20 exerted higher efficacy than sorafenib on tumour cell proliferation and angiogenesis. Conclusions Compared with its parent drug sorafenib, we found that 1118-20 possessed more potential on inhibition of angiogenesis and cancer cells growth. Inhibitory effect of 1118-20 on non-tumour liver cell HL-7702 was lower than that on hepatoma carcinoma cell HepG2. These results suggest that 1118-20 is a promising candidate compound that could be developed to a potent anticancer agent. [ABSTRACT FROM AUTHOR]

Objectives The goals were to investigate the mechanisms underlying the antiproliferative effects of bergamot essential oil ( BEO) and to identify the compounds mainly responsible for its SH- SY5Y cells growth rate inhibition. Methods Five BEO extractive fractions ( BEOs) differing in their chemical composition were used. Cell proliferation was determined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide ( MTT) and cell count assays. Trypan blue exclusion test and Annexin V/ PI staining were performed to assess their cytotoxic activity. Genotoxicity was detected by comet assay. The cell cycle was checked cytofluorimetrically. Reactive oxygen species ( ROS) and Δψm were measured fluorimetrically. Western blotting analyses for some apoptosis-related proteins were carried out. Key findings Treatment of SH- SY5Y cells with some types of BEOs decreased cell growth rate by a mechanism correlated to both apoptotic and necrotic cell death. Coloured BEOs act by increasing ROS generation, responsible for the drop in Δψm, and modulate p38 and extracellular signal-regulated kinases (ERK ½) mitogen-activated protein kinases, p53, Bcl-2 and Bax signalling pathways. Finally, we identify bergamottin and 5-geranyloxy-7-methoxycoumarin as the bioactive molecules that could play a pivotal role in the antiproliferative effects exerted by coloured BEOs. Conclusions Our study provides novel insights into the field of the antiproliferative effects of BEO, which could be exploited in the context of a multitarget pharmacological strategy. [ABSTRACT FROM AUTHOR]

Objectives Cadherin-11 ( CDH11) is an adhesion molecule that anchors β-catenin and is involved with various functions of synovial fibroblast cells ( SFCs) during the development of rheumatoid arthritis ( RA). However, the mechanism of CDH11 during RA-SFC proliferation is unclear. The aim of our study was to clarify the involvement of CDH11 and β-catenin signalling during proliferation. Methods IL-1β-induced and tumour necrosis factor-α ( TNF-α)-induced cell proliferation, with CDH11 siRNAs, β-catenin-specific siRNAs and a CDH11-neutralizing antibody, were assessed by 5-Bromo-2'-deoxy-uridine ELISA. Key findings Using CDH11 siRNAs, there were a 42% reduction in IL-1β-induced proliferation and a 64% reduction in β-catenin protein. When β-catenin siRNAs were applied, there was a 63% reduction in IL-1β-induced proliferation. The median effective concentration ( EC50) values for IL-1β-induced proliferation via CDH11-mediated β-catenin-dependent, total β-catenin-dependent and β-catenin-independent signalling were 0.0015, 0.016 and 0.18 ng/ml, respectively. Blocking CDH11 ligation with a CDH11-neutralizing antibody did not decrease IL-1β-induced proliferation. Conclusions CDH11-mediated β-catenin signalling was 42% involved in IL-1β-induced proliferation and had the highest susceptibility to IL-1β among the proliferative signallings analysed in this study. The mode of action for CDH11 during the cell proliferation was likely associated with a pool of β-catenin protein. In contrast, CDH11 and β-catenin were not involved in TNF-α-induced RA-SFC proliferation. [ABSTRACT FROM AUTHOR]

Objectives Baicalin, a natural flavone, has antithrombotic, antihyperlipidemic and antiinflammortory activity. It can also inhibit cancer cell proliferation and reduce brain cell apoptosis. This study aimed to elucidate the effect of baicalin on the excessive proliferation of human pulmonary arterial smooth muscle cells ( HPASMCs) induced by transforming growth factor-β1 ( TGF-β1) and to investigate the roles of hypoxia inducible factor-1α ( HIF-1α) and aryl hydrocarbon receptor ( AhR) in mediating this TGF-β1-induced excessive proliferation of HPASMCs. Methods TGF-β1-induced proliferation of HPASMCs was assayed using the CCK8 method. The cellular phenotype was identified by immunocytochemical staining. Expression of HIF-1α and AhR mRNA was determined by real-time quantitative PCR. Key findings TGF-β1 promoted significantly HPASMC proliferation ( P < 0.05) and induced a phenotypic switch from the contractile to synthetic type. Baicalin inhibited this TGF-β1-induced phenotypic switch and consequently the excessive growth of HPASMCs in a time-dependent and dose-dependent manner ( P < 0.05). Furthermore, baicalin attenuated the abnormal proliferation of HPASMCs through suppression of the HIF-1α and AhR pathways. Conclusions Our study shows that baicalin has the potential to be used as a novel drug in the treatment of pulmonary arterial hypertension pathology by antagonizing HIF-1α and AhR expression and subsequently decreasing HPASMC proliferation and the phenotypic switch. [ABSTRACT FROM AUTHOR]

Objectives Psoralea corylifolia is a plant widely used in traditional Chinese medicine, e.g. for its chemopreventive effect. To identify active substances responsible for this effect, we investigated pharmacological effects of 11 compounds isolated from the seeds of this plant (newly described substances: 7, 2′, 4′-trihydroxy-3-arylcoumarin and psoracoumestan). Methods The influence of distinct compounds on different signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) was screened via analysis of the activity of 24 protein kinases, mitogen activated protein kinase phosphorylation via Western blot, cytotoxicity was shown using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and determination of caspase activity. Oxidative stress was detected via 2′,7′-dichlorofluorescein fluorescence. Key findings Some compounds showed cytotoxic effects ( H4IIE, Hct116, C6 cells) mainly mediated via induction of apoptosis. Distinct compounds caused a strong inhibition of MAPK/ERK kinase ( MEK) phosphorylation, weak effects on extracellular-signal regulated kinase ( ERK) phosphorylation and no significant effect on p38 and c-Jun amino-terminal kinase. Corylifol C and, to a lesser extent, xanthoangelol are potent protein kinase inhibitors (inhibitory concentration 50% values for epidermal growth factor receptor ( EGFR): 1.1 and 4.4 × 10−6 μg/ml, respectively). Because EGFR, MEK and ERK are kinases involved in cellular proliferation, an inhibition of these enzymes may be useful to cause chemopreventive effects. Conclusions Distinct compounds isolated from P. corylifolia showed a high potential to influence cellular pathways, e.g. by inhibition of protein kinases that may be interesting for pharmacological purposes. [ABSTRACT FROM AUTHOR]

Objectives Cell proliferation and apoptosis play a major role in maintaining homeostasis and as such any disruption within these processes can lead to disease states. Apoptosis occurs in three non-distinct phases - induction, effector and degradation - and can be executed through both the extrinsic and intrinsic pathways in addition to recognised sub-pathways such as the p53 and lysosomal pathways. This review article highlights these pathways, incorporating an overview of the molecular regulators of apoptosis. Key findings These regulators include the prominent apoptotic players 'the caspases' in addition to the main regulators of the Bcl-2 family. Increased understanding of the physiological processes of apoptosis at the molecular level not only offers an insight in disease pathogenesis but, in addition, allows for the development of diagnostic, prognostic and therapeutic tools. Summary While apoptosis remains the key player in cellular death, other processes cannot be dismissed. Many other proteins, in addition to caspases, within apoptotic pathways have been identified. Research continues into establishing the precise aspects of their molecular mechanisms of action and inter-relationships. Inappropriate apoptosis due to dysregulation of cell death pathways provides a plethora of molecular checkpoints that can be targeted and modulated as part of therapeutic intervention. Increased research into these areas will prove useful for the design of novel chemotherapeutic drugs, an area that is particularly important due to increased risk of chemoresistance. [ABSTRACT FROM AUTHOR]

Objectives Novel lupane triterpenoids from Paullinia pinnata L., a Ghanaian plant traditionally used for wound healing, were examined for in-vitro fibroblast stimulatory activity using the 142BR cell line. Methods Bioactivity-guided isolation of the crude extract of P. pinnata L. was carried out in order to determine the nature of the compounds responsible for the stimulation of fibroblast proliferation. Key findings Two novel compounds were isolated and characterised, namely, 6β-(3′-methoxy-4′-hydroxybenzoyl)-lup-20(29)-ene-one ( 1) and 6β-(3′-methoxy-4′-hydroxybenzoyl)-lup-20(29)-ene-ol ( 2), together with three known compounds, friedelin ( 3), β-sitosterol ( 4) and β-sitosterol-3- d-glucoside ( 5). The methanol extract of the roots of P. pinnata caused a significant in-vitro increase (94%) in 142BR cell line proliferation at 20 µg/ml compared with the control. Conclusions Compounds 1 and 2, which were isolated from the active chloroform fraction, have not previously been reported and showed a dose-dependent increase in proliferation of 142BR cells up to 3 µ m; compounds 3, 4 and 5 had no effect on the 142BR cell line at the concentrations tested. [ABSTRACT FROM AUTHOR]

Objectives Glutathione S-transferases (GSTs) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases nitric oxide on metabolism by GST. O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antineoplastic activity. Methods We studied the effect of JS-K on angiogenesis in human umbilical vein endothelial cells (HUVECs), OPM1 multiple myeloma cells, chick aortic rings and in mice. Key findings JS-K inhibited the proliferation of HUVECs with a 50% inhibitory concentration (IC50) of 0.432, 0.466 and 0.505 μ m at 24, 48 and 72 h, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 μ m, respectively. JS-K inhibited cell migration at 5 h using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 μ m. In the chick aortic ring assay using VEGF or FGF-2 for vessel growth stimulation, 0.5 μ m JS-K completely inhibited vessel growth. JS-K inhibited tumour angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. Conclusions JS-K is a potent inhibitor of angiogenesis in vitro and tumour vessel growth in vivo. As such, it establishes a new class of antineoplastic agent that targets the malignant cells directly as well as their microenvironment. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the anti-inflammatory effects of Artemisia princeps extract in T cells and regulatory T cells stimulated by antigen. The study is investigated by enzyme-linked immunosorbent assay, cell proliferation analysis, and gas chromatography-mass spectrometry. Results show that A. princeps can be used in treating autoimmune diseases and the rejection of organ transplant.

Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)-induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II-induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto-oncogene c-fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real-time RT-PCR. VSMC cultures were verified by morphology and immunostaining with α-smooth muscle actin. Isorhynchophylline (0.1–10.0 μM) was not toxic to VSMCs, but markedly decreased Ang II (1.0 μM)-enhanced cell number and MTT intensity, and blocked cell transition from G0/G1 to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II-induced over-expression of c-fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang-II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c-fos, OPN and PCNA related to VMSC proliferation. [ABSTRACT FROM AUTHOR]