benzofurans has been researched along with Carcinoma--Squamous-Cell* in 21 studies
21 other study(ies) available for benzofurans and Carcinoma--Squamous-Cell
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Usnic acid induced changes in biomolecules and their association with apoptosis in squamous carcinoma (A-431) cells: A flow cytometry, FTIR and DLS spectroscopic study.
Topics: Amides; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA; Flow Cytometry; Humans; Spectroscopy, Fourier Transform Infrared | 2022 |
(+)-Usnic Acid Induces ROS-dependent Apoptosis via Inhibition of Mitochondria Respiratory Chain Complexes and Nrf2 Expression in Lung Squamous Cell Carcinoma.
Lung squamous cell carcinoma (LUSC) has a poor prognosis, in part due to poor therapeutic response and limited therapeutic alternatives. Lichens are symbiotic organisms, producing a variety of substances with multiple biological activities. (+)-Usnic acid, an important biologically active metabolite of lichens, has been shown to have high anti-cancer activity at low doses. However, there have been no reports regarding the effect of (+)-usnic acid on LUSC cells. This study found that (+)-usnic acid reduced viability and induced apoptosis in LUSC cells by reactive oxygen species (ROS) accumulation. (+)-Usnic acid induced mitochondria-derived ROS production via inhibition of complex I and complex III of the mitochondrial respiratory chain (MRC). Interestingly, the elimination of mitochondrial ROS by Mito-TEMPOL only partially reversed the effect of (+)-usnic acid on cellular ROS production. Further study showed that (+)-usnic acid also induced ROS production via reducing Nrf2 stability through disruption of the PI3K/Akt pathway. The in vitro and in vivo xenograft studies showed that combined treatment of (+)-usnic acid and paclitaxel synergistically suppressed LUSC cells. In conclusion, this study indicates that (+)-usnic acid induces apoptosis of LUSC cells through ROS accumulation, probably via disrupting the mitochondrial respiratory chain (MRC) and the PI3K/Akt/Nrf2 pathway. Therefore, although clinical use of (+)-usnic acid will be limited due to toxicity issues, derivatives thereof may turn out as promising anticancer candidates for adjuvant treatment of LUSC. Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Cell Line, Tumor; Electron Transport Chain Complex Proteins; Humans; Lung Neoplasms; Mice; Mitochondria; NF-E2-Related Factor 2; Paclitaxel; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Transplantation, Heterologous | 2020 |
Isolation of dihydrobenzofuran derivatives from ethnomedicinal species Polygonum barbatum as anticancer compounds.
Ethnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum.. The column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P. barbatum, the isolated compounds (1-3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity.. Three dihydrobenzofuran derivatives (1-3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC. Based on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate. Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Benzofurans; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Humans; Polygonum | 2019 |
Evaluation of Tumor Cell-Tumor Microenvironment Component Interactions as Potential Predictors of Patient Response to Napabucasin.
Topics: Benzofurans; Cancer-Associated Fibroblasts; Carcinogenesis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Lineage; Coculture Techniques; Gene Expression Regulation, Neoplastic; Humans; Hypopharyngeal Neoplasms; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; STAT3 Transcription Factor; Tumor Microenvironment | 2019 |
Salvianolic acid B inhibits glycolysis in oral squamous cell carcinoma via targeting PI3K/AKT/HIF-1α signaling pathway.
Our previous study demonstrated a progressive glycolytic perturbation during the course of DMBA-induced hamster oral carcinogenesis, which was attenuated by salvianolic acid B (Sal-B) treatment along with decreased incidences of oral squamous cell carcinoma (OSCC) formation. It was proposed that metabolic modulation should be an additional mode of action attributable to Sal-B's anti-carcinogenic activity. However, the molecular mechanisms underlying Sal-B-induced metabolic modulation function remained elusive. In the present study, we performed next-generation sequencing (NGS) profiling in the same animal model and found Sal-B treatment evoked a general downregulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and hypoxia inducible factor 1α subunit (HIF-1α) signaling pathways, which might contribute to Sal-B's metabolic modulation activity. The inhibitory effects of Sal-B on aerobic glycolysis, as well as PI3K/AKT and HIF-1α signaling pathways, were validated in two well-characterized OSCC cell lines (Cal27 and HN4), and premalignant oral Leuk1 cells and Sal-B treatment led to elevation of the loss of mitochondrial membrane potential (MMP), increased cell apoptosis, and reduced abilities of colony formation. Rescue assays suggested that compared with Sal-B treatment group, Akt or hif-1a overexpression attenuated the inhibitory effect of Sal-B on glucose uptake and intracellular lactate level. Taken together, our results suggested that Sal-B modulated aberrant glucose metabolism via the PI3K/AKT/HIF-1α signaling pathways, which might contribute to the anti-carcinogenic activity of Sal-B. Topics: Animals; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Clone Cells; Disease Models, Animal; Glucose; Glycolysis; Hypoxia-Inducible Factor 1, alpha Subunit; Lactates; Male; Membrane Potential, Mitochondrial; Mesocricetus; Models, Biological; Mouth Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction | 2018 |
Quantitative Structure-Cytotoxicity Relationship of Aurones.
Seventeen aurones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor-specificity, in order to find their new biological activities.. Cytotoxicity against three human oral squamous cell carcinoma cell lines and three oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC. Sixteen out of seventeen aurones showed relatively higher cytotoxicity and tumor specificity. Among them, (2Z)-2-[(4-hydroxyphenyl)methylene]-3(2H)-benzofuranone [. Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs. Topics: Antineoplastic Agents; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Cell Proliferation; Child; Female; Humans; Molecular Structure; Mouth Neoplasms; Quantitative Structure-Activity Relationship; Tumor Cells, Cultured | 2017 |
Cellular uptake and anticancer activity of salvianolic acid B phospholipid complex loaded nanoparticles in head and neck cancer and precancer cells.
Salvianolic acid B (SalB) was demonstrated to be a promising chemopreventive agent for head and neck squamous cell carcinoma (HNSCC) in the previous studies by our and other research institution, but the properties like low efficacy, poor systemic delivery, and low bioavailability has hampered its clinical applications. To continue our research program focused on the use of natural compounds on cancer chemoprevention, we propose a first example of phospholipid complex loaded nanoparticles (PLC-NPs) encapsulating SalB as a potential carrier for intervention of HNSCC (HN13, HN30) cells and precancer Leuk1 cells in this study. Qualitative and quantitive studies of cellular uptake showed that intracellular accumulation of SalB was significantly higher when HN13, HN30 and Leuk1 cells were incubated with SalB-PLC-NPs complex (nano-SalB) as against free-SalB. Cell viability assay revealed that the cell growth of HN13 and HN30 cells was significantly inhibited of 56.1% and 29.3%, respectively, for nano-SalB compared to an equivalent amount of free-SalB (P<0.001). Moreover, cell cycle and apoptosis assay showed that a clear trend of cell cycle arrest and induction of apoptosis was also observed within the HNSCC cells treated with nano-SalB. Collectively, this study demonstrated that nano-SalB was significantly more potent had an anticancer effect against HNSCC cells, which serves as the first step toward establishing SalB nano-formulations as promising cancer chemopreventive agents. The current study could pave a new way for the development of drugs that target HNSCC in the future. Topics: Antineoplastic Agents; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Cell Cycle; Cell Proliferation; Drugs, Chinese Herbal; Head and Neck Neoplasms; Humans; Nanoparticles; Precancerous Conditions; Tumor Cells, Cultured | 2016 |
Expression of Nur77 induced by an n-butylidenephthalide derivative promotes apoptosis and inhibits cell growth in oral squamous cell carcinoma.
In spite of numerous advances, the 5-year survival rate for head and neck squamous cell cancer has remained largely stagnant and few new anti-tumor drugs have been developed. PCH4, a derivative of n-butylidenephthalide, has been investigated for its anti-tumor effects on oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the anti-tumor mechanism of a potential target gene, Nur77, in OSCC cells, which can be induced by PCH4 treatment. Data show that PCH4 promoted Nur77 translocation from the nucleus to the cytoplasm and induced cell apoptosis in OSCC cells. When Nur77 translocation was blocked, the degree of tumor apoptosis caused by PCH4 was significantly inhibited (p < 0.05). Within the MAPK pathway, PCH4 only induced JNK phosphorylation. Furthermore, treatment with a JNK inhibitor significantly reduced PCH4-induced apoptosis (p < 0.05) and decreased PCH4-induced Nur77 expression (p < 0.05). In a xenograft animal model, administration of PCH4 also showed anti-tumor effects. We have demonstrated that OSCC cells are sensitive to PCH4 and that Nur77 protein translocation from the nucleus to the cytoplasm might be associated with the induction of apoptosis by PCH4. These results indicate that PCH4 may serve as a potential anti-tumor drug for OSCC therapy. Topics: Active Transport, Cell Nucleus; Animals; Antineoplastic Agents; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Ethylamines; Female; Humans; JNK Mitogen-Activated Protein Kinases; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Nuclear Receptor Subfamily 4, Group A, Member 1; Phosphorylation; Phthalic Anhydrides; Protein Kinase Inhibitors; RNA, Messenger; Time Factors; Tumor Burden; Up-Regulation; Xenograft Model Antitumor Assays | 2012 |
Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B.
Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition.. Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data.. Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated.. Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma. Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Benzofurans; Carcinoma, Squamous Cell; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Drugs, Chinese Herbal; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leukoplakia; Matrix Metalloproteinase 9; Mouth Neoplasms; Oligonucleotide Array Sequence Analysis; Phytotherapy; Reverse Transcriptase Polymerase Chain Reaction; Salvia miltiorrhiza; Thrombospondins; Tumor Necrosis Factor-alpha; Up-Regulation | 2011 |
Combination effects of salvianolic acid B with low-dose celecoxib on inhibition of head and neck squamous cell carcinoma growth in vitro and in vivo.
Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, JHU-011, JHU-013, and JHU-022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single-agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was associated with profound inhibition of COX-2 and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low-dose celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development. Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzofurans; Carcinoma, Squamous Cell; Celecoxib; Cell Division; Cell Line, Tumor; Cyclooxygenase 2 Inhibitors; Dinoprostone; Drug Synergism; Head and Neck Neoplasms; Humans; In Situ Nick-End Labeling; Male; Mice; Mice, Nude; Pyrazoles; Salvia miltiorrhiza; Sulfonamides; Xenograft Model Antitumor Assays | 2010 |
Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways.
Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long-term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from S. miltiorrhiza Bge by solvent extraction followed by 2 chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC(50) of 18 and 50 microM, respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80 mg/kg/day) or celecoxib (5 mg/kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were significantly lower than those in celecoxib treated or untreated control groups (p < 0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E(2) synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment. Topics: Animals; Apoptosis; Benzofurans; Blotting, Western; Carcinoma, Squamous Cell; Caspases; Cells, Cultured; Colony-Forming Units Assay; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Drugs, Chinese Herbal; Female; Flow Cytometry; Head and Neck Neoplasms; Humans; In Vitro Techniques; Keratinocytes; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Mucosa; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salvia miltiorrhiza; Survival Rate; Transplantation, Heterologous | 2009 |
Reproductive lesions in female Harlan Sprague-Dawley rats following two-year oral treatment with dioxin and dioxin-like compounds.
Results from previously published animal studies suggest that prenatal and postnatal exposure to dioxin and dioxin-like compounds (DLCs) may profoundly affect the reproductive system of both sexes via endocrine disruption. In the present work, we evaluate the toxicity and carcinogenicity of various DLCs, with an emphasis on their effect on the reproductive organs, induced by chronic exposure of female adult Harlan Sprague-Dawley rats. This investigation represents part of an initiative of the National Toxicology Program to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. For fourteen, thirty-one, or fifty-three weeks or for two years, animals were administered by gavage 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); 2,3',4,4',5-pentachlorobiphenyl (PCB118); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and PCB118. The ranges of treatment-related changes in the reproductive system included chronic active inflammation in the ovary that occurred in the 1,000 and 3,000 microg/kg core groups (two-year exposure) of PCB153 and in the 300 ng/3,000 microg/kg core group of binary mixture of PCB126 and PCB153. Increases in the incidence of acute and/or chronic active inflammation of the uterus were observed in all dosed groups, including the stop-exposure group (withdrawal after thirty-week exposure) of PeCDF and the 1,000 microg/kg and/or higher group dosed with PCB153. The incidence of cystic endometrial hyperplasia was marginally increased in the 92 PeCDF ng/kg group at two years. The incidence of squamous metaplasia was significantly increased in the 44 ng/kg and higher dose group, including the stop-exposure group. The incidence of uterine squamous cell carcinoma was significantly or marginally increased in the 6 ng/kg core and 100 ng/kg stop-exposure groups of TCDD and in the 300 ng/300 microg/kg core group that received the binary mixture of PCB126 and 153. The incidence of uterine carcinoma was marginally increased in the 92 ng/kg PeCDF group at two years and clearly increased in the 1,000 and 4,600 microg/kg PCB118 core group and the 4,600 microg/kg stop group. In the studies of PCB 126, the tertiary mixture, and the binary mixture of PCB126 and PCB118, no increased incidence of any change occurr Topics: Administration, Oral; Animals; Benzofurans; Carcinogens; Carcinoma, Squamous Cell; Dioxins; Endometrial Hyperplasia; Female; Metaplasia; Ovary; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Rats; Rats, Sprague-Dawley; Reproduction; Toxicity Tests; Uterine Neoplasms; Uterus | 2009 |
Activated cholinergic signaling provides a target in squamous cell lung carcinoma.
The binding of exogenous nicotine to nicotinic acetylcholine (ACh) receptors (nAChR) and the binding of endogenous ACh to both nAChR and muscarinic ACh receptors (mAChR) stimulate growth of both small cell and non-small cell lung carcinomas. Understanding how cholinergic signaling is up-regulated in lung cancer may suggest new therapeutic approaches. Analysis of 28 squamous cell lung carcinomas (SCC) showed increased levels of alpha5 and beta3 nAChR mRNA and increased levels of ACh associated with increased levels of choline acetyltransferase mRNA and decreased cholinesterase mRNAs. Lynx1, an allosteric inhibitor of nAChR activity, was also decreased in SCC. Thus, cholinergic signaling is broadly increased in SCC caused by increased levels of receptors, increased levels of ligands, and decreased levels of receptor inhibitors. Partially explaining the cholinergic up-regulation seen in SCC, incubation of the H520 SCC cell line with nicotine increased levels of ACh secretion, increased expression of nAChR, and, as measured by electrophysiologic recording, increased activity of the expressed nAChR. Consistent with these effects, nicotine stimulated proliferation of H520 cells. One approach to blocking proliferative effects of nicotine and ACh on growth of lung cancers may be through M3 mAChR antagonists, which can limit the activation of mitogen-activated protein kinase that is caused by both nicotinic and muscarinic signaling. This was tested with the M3-selective muscarinic antagonist darifenacin. Darifenacin blocked nicotine-stimulated H520 growth in vitro and also blocked H520 growth in nude mice in vivo. Thus, cholinergic signaling is broadly up-regulated in SCC and blocking cholinergic signaling can limit basal and nicotine-stimulated growth of SCC. Topics: Acetylcholine; Adaptor Proteins, Signal Transducing; Animals; Benzofurans; Blotting, Western; Calcium; Carcinoma, Squamous Cell; Cell Proliferation; Cells, Cultured; Choline O-Acetyltransferase; Electrophysiology; GPI-Linked Proteins; Humans; Lung; Lung Neoplasms; Male; Membrane Glycoproteins; Mice; Mice, Nude; Muscarinic Antagonists; Nicotine; Phosphorylation; Pyrrolidines; Receptor, Muscarinic M3; Receptors, Nicotinic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Vesicular Acetylcholine Transport Proteins | 2008 |
The preventive effect of salvianolic acid B on malignant transformation of DMBA-induced oral premalignant lesion in hamsters.
Salvia miltiorrhiza (SM) has been used clinically in Asian countries to improve the microcirculation in the human body. Salvianolic acid B (Sal B), a pure compound extracted from SM, has been reported to be effective against fibrosis and ischemia-reperfusion injury, possibly through its anti-lipid peroxidation action. But the effect of Sal B on oral premalignant lesion and oral carcinogenesis remains unexplored. It is our interest to investigate the chemopreventive effect of Sal B on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters with respect to angiogenesis. Seventy male Syrian golden hamsters were randomly divided into five groups, with two of 20 and three of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in Groups A and B, while animals in Group C were painted with acetone, three times a week for 6 weeks. For the next 18 weeks, animals in Groups B and D received Sal B daily (10 mg/kg body wt/day) by gavage, animals in Groups A and C received same volume of saline. Animals in Group E received no treatment and served as blank control. At the end of the experiment, animals were killed and tissue samples were collected for histopathological and immunohistochemical examinations. The results showed that Sal B significantly decreased the squamous cell carcinoma (SCC) incidence from 64.7 (11/17) to 16.7% (3/18) (P=0.004); angiogenesis was inhibited in dysplasia and SCC (P<0.01), with a simultaneous decrease in the immunostaining of hypoxia-inducible factor 1alpha and vascular endothelium growth factor protein (P<0.05). The results suggested that Sal B had inhibitory effect against the malignant transformation of oral precancerous lesion and such inhibition may be related to the inhibition of angiogenesis. Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; Benzofurans; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chemoprevention; Cricetinae; Male; Mesocricetus; Mouth Neoplasms; Neovascularization, Pathologic; Precancerous Conditions; Random Allocation | 2006 |
Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds.
We evaluated gingival toxicities induced by chronic exposure of female Harlan Sprague-Dawley rats to dioxin and dioxin-like compounds (DLCs) and compared them to similarly induced oral lesions reported in the literature. This investigation represents part of an ongoing initiative of the National Toxicology Program to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. For two years, animals were administered by gavage 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99:1) alone. A full complement of tissues, including the palate with teeth, was examined microscopically. In the groups treated with TCDD and the mixtures of TCDD, PCB126, and PeCDF; PCB126 and 153; and PCB126 and 118, the incidences of gingival squamous hyperplasia increased significantly. Moreover, in the groups treated with TCDD, PCB126, and the mixture of PCB126 and 153, squamous cell carcinoma (SCC) in the oral cavity increased significantly. This investigation constitutes the first report documenting that chronic administration of dioxin-like PCBs can induce gingival SCC in rats. These results indicate that dioxin and DLCs target the gingiva of the oral cavity, in particular the junctional epithelium of molars. Topics: Administration, Oral; Animals; Benzofurans; Carcinogenicity Tests; Carcinoma, Squamous Cell; Dioxins; Dose-Response Relationship, Drug; Drug Synergism; Female; Gingiva; Gingival Neoplasms; Hyperplasia; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Rats; Rats, Sprague-Dawley; Time Factors | 2005 |
Exposure to soil contaminated with an environmental PCB/PCDD/PCDF mixture modulates ultraviolet radiation-induced non-melanoma skin carcinogenesis in the Crl:SKH1-hrBR hairless mouse.
Chlorinated aromatic contaminants are active in carcinogenic processes within the skin and may have the potential to modulate ultraviolet radiation (UV)-induced skin carcinogenesis. Exposure to a complex environmental PCB/PCDD/PCDF mixture (polychlorinated biphenyls/polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans) during the irradiation phase of photocarcinogenesis was associated with significant (P < or = 0.001) reductions in papilloma incidence and squamous cell carcinoma multiplicity at irradiated skin sites. This protective effect was associated with significantly (P < 0.0001) reduced chronic epidermal thickening in UV and contaminant-exposed mice compared with mice exposed to UV only. Contaminant exposure was also associated with increased UV absorbance of skin methanol extracts implying a sunscreen-like effect. Topics: Animals; Benzofurans; Carcinoma, Squamous Cell; Dibenzofurans, Polychlorinated; Environmental Pollutants; Female; Methanol; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Papilloma; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Skin; Skin Neoplasms; Soil Pollutants; Ultraviolet Rays | 2003 |
Total synthesis and biological properties of novel antineoplastic (chloromethyl)furanoindolines: an asymmetric hydroboration mediated synthesis of the alkylation subunits.
1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to an asymmetric synthesis of the CFI alkylation subunit has been achieved by the implementation of an asymmetric hydroboration reaction of an intermediate 3-methyleneindoline (13). Extension to the asymmetric synthesis of the CBI and CI alkylation subunits is presented. The demonstration and comparative study of the sequence-selective DNA alkylation properties of the CFI-based agents are detailed, and the preliminary in vitro and in vivo antineoplastic properties of these agents in the human epidermoid cell lung carcinoma (T222) are described. Topics: Alkylation; Animals; Antineoplastic Agents; Base Sequence; Benzofurans; Boron Compounds; Carcinoma, Squamous Cell; Cyclohexanecarboxylic Acids; Cyclohexenes; DNA; Drug Screening Assays, Antitumor; Duocarmycins; Female; Furans; Humans; Indoles; Leucomycins; Lung Neoplasms; Mice; Mice, Nude; Molecular Sequence Data; Tumor Cells, Cultured | 1994 |
Evaluation of the antineoplastic activity of adozelesin alone and in combination with 5-aza-2'-deoxycytidine and cytosine arabinoside on DLD-1 human colon carcinoma cells.
Adozelesin (Ado), a CC-1065 analog, shows significant antineoplastic activity in vivo against several types of murine tumors and human tumor xenografts. Ado is a DNA alkylating agent. One objective of this study was to investigate the cytotoxic action of Ado against the human colon (HT-29, DLD-1) and the lung (SK) carcinoma cell lines. The concentrations of Ado that produced 50% cell kill for a 4 and 24 h exposure were in the range of 0.001-0.02 ng/ml for both colon and lung carcinoma cells, indicating that this analog was a very potent cytotoxic agent. Since most clinical regimens for tumor therapy consist of several drugs, we investigated the antineoplastic action of Ado in combination with 5-aza-2'-deoxycytidine (5-Aza-CdR), a potent inhibitor of DNA methylation or cytosine arabinoside (Ara-C), a potent inhibitor of DNA synthesis. The Ado plus 5-Aza-CdR combination showed a synergistic effect on cytotoxicity of DLD-1 colon carcinoma cells for both a 6 and 24 h exposure. However, combination of Ado and Ara-C for a 6 h exposure showed an antagonistic effect, whereas a 24 h exposure showed a synergistic effect. These preclinical results provide some preliminary data on possible drugs that can be selected for use in combination with Ado in future clinical trials in patients with cancer. Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Benzofurans; Carcinoma, Squamous Cell; Cell Division; Colonic Neoplasms; Cyclohexanecarboxylic Acids; Cyclohexenes; Cytarabine; Decitabine; DNA, Neoplasm; Drug Screening Assays, Antitumor; Duocarmycins; Humans; Indoles; Lung Neoplasms; Time Factors; Tumor Cells, Cultured | 1993 |
Relative toxicity and tumor-promoting ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) in hairless mice.
2,3,7,8-Tetrachlorodibenzo-p-dixoin 2,3,4,7,8-pentachlorodibenzofuran (PCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) are highly toxic members of a class of environmental contaminants, the polychlorinated aromatic hydrocarbons (PCAH), which exhibit a similar and highly characteristic spectrum of toxic effects. For purposes of risk assessment, it is important to be able to make accurate estimates of the relative potency of these and related compounds. Previous investigations have indicated that, in acute exposure or in vitro studies, PCDF is approximately 0.1 times as toxic and HCDF is approximately 0.01 times as toxic as TCDD. In this study, we compared the relative toxicity and tumor-promoting abilities of TCDD, PCDF, and HCDF in hairless mouse skin. Female hairless mice (HRS/J hr/hr) were treated dermally with the initiator MNNG, then dosed twice weekly for 20 weeks with acetone, TCDD (2.5-10 ng/mouse/dose), PCDF (25-100 ng/mouse/dose), or HCDF (250-1000 ng/mouse/dose) as promoter. TCDD, PCDF, and HCDF were all potent promoters for the induction of squamous cell papillomas. There was, however, no difference in the incidence or multiplicity of papilloma formation between groups. The same doses of the three PCAH, in the absence of initiator, induced no skin papillomas. TCDD produced a significant increase in liver:body weight ratio (p less than 0.001) at all doses and a decrease in thymus:body weight ratio at a dose of 10 ng (p less than 0.001). Mice treated with PCDF and HCDF had marked thymic and splenic involution, liver hypertrophy, mucous cell hyperplasia in the fundic portion of the glandular stomach, and loss of body weight. PCDF and HCDF produced a greater incidence and severity of dermatotoxic effects than TCDD. Based on data for dermal toxicity and changes in body weight and organ weights, PCDF is estimated to be 0.2 to 0.4 times, and HCDF 0.08 to 0.16 times, as toxic as TCDD following repeated dermal exposure. Therefore, toxic equivalence factors generated using data from acute and/or in vitro studies may underestimate the risk from repeated low-dose exposures to these compounds. Topics: Animals; Benzofurans; Carcinoma, Squamous Cell; Dioxins; Female; Hypertrophy; Liver; Mice; Mice, Hairless; Papilloma; Polychlorinated Dibenzodioxins; Skin; Skin Diseases; Skin Neoplasms | 1990 |
[Influences of polychlorinated dibenzofuran on experimental carcinogenesis in mice].
To ascertain whether 2,3,4,7,8-pentachlorodibenzofuran (PCDF) has the possibility of cocarcinogen, three different concentrations of 0.5, 1 and 5 ppm PCDF was evaluated in the course of experimental carcinogenesis in mice. Concerning the difference of total number of tumors occurred among the groups of mice with various treatments, the mice treated with 0.5 ppm PCDF and 20-methylcholanthrene (MC) have produced twice as many tumors as those of the other groups. Then the adequate concentration of PCDF to be a promoter was supposed to be 0.5 ppm. Two kinds of tumors were seen in mice which were treated by MC with or without PCDF, and there was no difference of tumors between the groups by appearance and pathologically. One is a benign papilloma, and the other is a squamous cell carcinoma which tends to keratinize and looks like a keratoacanthoma. The latter had a tendency to arise much more four weeks after the treatments had been done, even though the number of the former increased gradually. There was no evidence that PCDF of these concentrations could permeate through the skin and could be toxic. Furthermore PCDF seemed to neither stay nor act directly on the follicular epithelium, since there was no acne formation on the back skin of mice. One of the possible factors to cause malignant changes of epidermal cells was supposed to be a prolonged inflammation of the skin. Topics: Animals; Benzofurans; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Methylcholanthrene; Mice; Skin Neoplasms | 1989 |
[The effectiveness of chemotherapy of radiation skin cancer].
Topics: Adult; Aged; Antineoplastic Agents; Benzoates; Benzofurans; Cacao; Caffeine; Carcinoma, Squamous Cell; Castor Oil; Colchicine; Female; Humans; Male; Middle Aged; Neoplasms, Radiation-Induced; Ointments; Plant Extracts; Skin; Skin Neoplasms; Uracil | 1972 |