Showing papers on "Arecoline published in 2008"

Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2 -1195G>a polymorphism reveal risk of oral cancer

Abstract: Because the mRNA expression of cyclooxygenase-2 (COX-2) is up-regulated by arecoline in human gingival fibroblasts, as shown in our previous study, we further investigated the mRNA expression level of COX-2 and its upstream effectors in three oral epithelial carcinoma cell lines (KB, SAS, and Ca9-22) by using areca nut extract (ANE) and saliva-reacted ANE (sANE). A case-control study of 377 oral squamous cell carcinoma (OSCC) patients and 442 controls was conducted to evaluate the gene-environment interaction between COX-2 promoter polymorphisms and substance use of alcohol, betel quid, and cigarettes (ABC) in risk of OSCC. The heterogeneous characteristics of the oral site and the COX-2 -1195G>A polymorphism in these cell lines showed diverse inflammatory response (KB>>Ca9-22>SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-kappaB activation. In the case-control study, betel chewing [adjusted odds ratios (aOR), 42.2] posed a much higher risk of OSCC than alcohol drinking and cigarette smoking (aORs, 2.4 and 1.8, respectively), whereas the COX-2 -1195A/A homozygote presented a potential genetic risk (OR, 1.55). The strongest joint effect for OSCC was seen in betel chewers with -1195A/A homozygote (aOR, 79.44). In the non-betel chewing group, the -1195A/G and A/A genotypes together with the combined use of alcohol and cigarettes increased risk to 15.1-fold and 32.1-fold, respectively, compared with the G/G genotype without substance use. Taken together, these findings illustrate a valuable insight into the potential role of the COX-2 promoter region in contributing to the development of betel-related OSCC, including ANE/sANE-induced transcriptional effects and enhanced joint effects of COX-2 -1195A allele with substance use of ABC.

Availability and characteristics of betel products in the u.s

Abstract: Betel use involves oral placement of shards of areca nut (Areca catechu palm seed containing the cholinergic agonist arecoline) wrapped with slaked lime in a betel leaf (Piper betle plant) or various chopped or powdered products containing areca nut and/or parts of the betel plant. Additives to this mixture include catechu (areca palm extract), spices/sweeteners (e.g., saccharin, cloves), and/or tobacco. Betel use is most common in Asia and East India; however, little is known about the availability and characteristics of these products outside of this region. Thus, a representative sample of betel products and additives was purchased in the Richmond, Virginia area. Five venues were visited between March and May, 2006. Products successfully purchased were those containing betel alone (seven), betel/tobacco (three), tobacco alone (four), and additives (four). Most betel products listed ingredients on the packaging, though some did not explicitly distinguish between those with versus without tobacc...

The upregulation of heat shock protein 47 expression in human buccal fibroblasts stimulated with arecoline

Abstract: Background: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HSP47 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further to explore the potential mechanisms that may lead to induce HSP47 expression. Methods: The mRNA levels of HSP47 from fibroblasts cultured from 20 OSF and 10 normal buccal mucosal fibroblasts (BMFs) were evaluated by reverse transcription polymerase chain reaction. The effect of arecoline, the major areca nut alkaloid, was added to explore the potential mechanisms that may lead to induce HSP47 expression. Furthermore, mitogen-activated protein kinase kinase (MEK) inhibitor U0126, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, p38 inhibitor SB203580, cyclo-oxygenase-2 (COX-2) inhibitor NS-398, and glutathione precursor N-acetyl-l-cysteine were added to find the possible mechanisms. Results: OSF demonstrated significantly higher HSP47 mRNA expression than BMFs (P < 0.001). Arecoline was also found to elevate HSP47 mRNA expression in a dose-dependent manner (P < 0.05). The amount of HSP47 was about 3.7-fold at a concentration level of 80 μg/ml arecoline when compared with control (P < 0.05). In addition, pre-treatment with pharmacologic agents markedly inhibited the arecoline-induced HSP47 mRNA expression (P < 0.05). Conclusions: Taken together, HSP47 is significantly upregulated in OSF from areca quid chewers and HSP47 expression induced by arecoline in fibroblasts may be mediated by MEK, PI3K, and COX-2 signal transduction pathways.

Effects of arecoline on testosterone release in rats.

Abstract: Arecoline is one of the major components of betel nuts, which have been consumed as chewing gum in Southeast Asia. In this study, the effects of arecoline on testosterone (T) secretion were explore...

Autophagy induction by a natural ingredient of areca nut.

Abstract: We recently identified an autophagy-inducing areca nut ingredient (AIAI) in the partially purified 30-100 kDa fraction of areca nut extract (ANE), designated as ANE 30-100K. Before disintegration, most ANE 30-100K-treated cells exhibit rounding morphology, cytoplasmic clearance, and nuclear shrinkage, distinct from arecoline- and cisplatin-induced cellular apoptosis. This unique death pattern is verified to be autophagy by LC3-I cleavage, acidic vesicles, and autophagic vacuoles. As analyzed by Molish's Test, Selinowaff's Test, and thin-layer chromatography, most of the ANE 30-100K constituents are carbohydrates, whereas the protein content of this fraction is less than 1% as assessed by protein assay reagent. The cytotoxicity of ANE 30-100K is further shown to be sensitive to cellulase and proteinase K digestion suggesting AIAI in ANE 30-100K to be a proteoglycan (or glycoprotein). Thus, although ANE contains apoptosis-inducing ingredients such as arecoline, it predominantly triggers autophagic cell death by this natural AIAI.

Arecoline and the 30-100 kDa fraction of areca nut extract differentially regulate mTOR and respectively induce apoptosis and autophagy: a pilot study.

Abstract: Areca nut (AN) is recognized as a human carcinogen; however, few studies of the cytotoxic effects of AN ingredients on cells have been reported. In Taiwan, AN, lime and inflorescence of Piper betle are the common components of betel quid (BQ). We recently noticed that extract of AN (ANE), but not those of lime and inflorescence of Piper betle, induces rounding cell morphology and nuclear shrinkage in different types of carcinoma cells. In this study, the rounding cell activity was first traced to the partially purified ≥10 kDa fraction (ANE ≥ 10 K) and subsequently to the 30–100 kDa fraction (ANE 30–100 K). ANE and ANE ≥10 K stimulated nuclear shrinkage (P < 0.001 in both cases) and the clearance of the cytoplasm. ANE, ANE ≥ 10 K, and ANE 30–100 K induced the cleavage of LC3-I (P < 0.05, 0.01, and 0.05, respectively) and the emergence of autophagic vacuoles (AVs) and acidic vesicles. On the other hand, arecoline (Are, the major alkaloid of AN) triggered caspase-3 activation, peri-nuclear chromatin condensation, and micronucleation. Meanwhile, ANE 30–100 K, but not Are, inhibited the phosphorylation of the mammalian target of rapamycin (mTOR)-Ser2448. In conclusion, this study demonstrates that different AN ingredients exerting differential impact on mTOR-Ser2448 phosphorylation are capable of triggering apoptosis and autophagy.

Involvement of ionotropic glutamate receptors in the appearance of arecoline tremor in mice.

Abstract: Administration of the muscarinic cholinoreceptor agonist arecoline (6 mg/kg, s.c.) to mice induced long-lasting tremor. The ability of non-competitive antagonists of ionotropic glutamate receptors to suppress the onset of tremor was studied. These antagonists, i.e., adamantane and phenylcyclohexyl derivatives, selectively blocked NMDA-type receptor channels (monocations) or both NMDA-and AMPA-type channels (dications). Both types of blocker weakened arecoline tremor, though the dose-response relationships were different for mono-and dications. The effects of dications appeared only at low blocker doses (0.0001–0.01 µmol/kg) but gradually disappeared on dose elevation. These data lead to the conclusion that the mechanism of pathogenesis of arecoline tremor predominantly involves NMDA-type receptors. Moderate blockade of AMPA-type receptors could potentiate the preventive effect of mixed-action antagonists (anti-NMDA + anti-AMPA), though predominance of blocking action against AMPA-type receptors prevented this effect.

Effect of novel N-arylurea- substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s dementia models

Abstract: A series of novel, potent, and selective muscarinic receptor 1 agonists (M1 receptor agonists) that employ a key N-substituted morpholine Arecoline moiety has been synthesized as part of research effort for the therapy of Alzheimer's diseases. The ester group of arecoline (which is reported as muscarinic agonist) has been replaced by N-substituted morpholine ring. The structure activity relationship reveals that the electron donating 4-substituted sulfonyl derivatives (9a, 9b, 9c, and 9e) on the nitrogen atom of the morpholine ring increases the affinity of M1 receptor binding 50- to 80-fold greater than the corresponding arecoline. Other derivatives also showed considerable M1 receptor binding affinity. (C) 2008 Elsevier Ltd. All rights reserved.

Aqueous extract of betel nut-induced adducts on pMTa4 DNA acquires stability in the presence of Na+ and K+ ions.

Abstract: Betel nut (BN), a natural carcinogen to humans, is used as a masticator across the globe by a large segment of the human population. The primary carcinogens of BN are alkaloids, in particular arecoline. Upon nitrosation, arecoline can potentially interact with DNA, forming adducts and initiating carcinogenesis. Though considerable evidence exists in support of the carcinogenicity of BN, the molecular mechanism of its induction of carcinogenesis is unknown. This investigation was undertaken to directly demonstrate adduct formation on DNA and to study its characteristics, such as its frequency of formation and stability. A plasmid DNA construct, pMTa4, was chosen to determine the stoichiometry and dynamics of adduct formation. This construct was exposed to aqueous extract of betel nut (AEBN) in vitro and in vivo and analyzed. Spectrophotometric analysis revealed a significant red shift in the pMTa4 DNA spectrum. The gel electrophoretic mobility of pMTa4 DNA was also retarded in an AEBN dose- and exposure time-dependent manner, indicating BN-specific adduct formation on the DNA. These results conclusively demonstrate that adducts are formed on DNA by BN extract, and suggest that one AEBN-induced adduct was formed every 3 NT on pMTa4 DNA under the experimental conditions. Trace amounts of monovalent cations, such as Na+ or K+ ion (≥0.5 mmol), conferred stability to the adducts on DNA, which were otherwise unstable beyond 24 h.

Expression of Matrix Metalloproteinases in Oral Cancer Patients Who Are Betel Quid Users

Abstract: The rate of squamous cell carcinoma (SCC) is the highest among oral cancers, and most of these patients have chewed betel nuts for a long time. Betel nut chewing has been proven to cause oral cancer. During tumor invasion and proliferation, matrix metalloproteinases (MMPs) family are some of the most important factors. MMPs can remodel peripheral tissues of tumors, and their expression can be induced during interactions among tumor cells, the extracellular matrix (ECM), and inflammatory cells. Thus the up- and downregulated expressions of MMPs significantly differ when applied to predicting tumor cell invasion and transfer. The overexpression of some MMPs was associated with oral cancer occurrence, proliferation, lymph node metastasis, and prognosis in recent studies. The Department of Oral and Maxillofacial Surgery of Chi-Mei Medical Center (Tainan, Taiwan) has particularly studied MMP expressions in patient, associated with betel nut chewing. Significant increases in MMP-1, -2, -3, -8, -9, and -28 expression in oral cancer patients with betel nut chewing habit have recently been found in our studies and reported in other papers. Betel nut extract (ANE) and arecoline are known to trigger MMP expression signals based on MEK/ERK and P1-3K signal transduction expression intensities and MMP production increments. This paper collected and analysed our data of MMPs studies. Our findings show the correspondence with other researchers’ reports. We think that these MMPs can be considered to be used as oral cancer cell markers and can be used to predict cancer prognosis.