RESUMO
The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.
Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteína Proto-Oncogênica N-Myc , Recidiva Local de Neoplasia , Proto-Oncogene Mas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/patologia , Proteína Proto-Oncogênica N-Myc/genética , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/sangue , PrognósticoRESUMO
BACKGROUND: Studies have shown that hepatitis B virus (HBV)-associated B-cell non-Hodgkin lymphoma (NHL) constitutes a unique subgroup with distinct clinical features. It still leaves open the question of whether the integration of HBV DNA into the B-cell genome is a causal mechanism in the development of lymphoma. METHODS: Using the hybridisation capture-based next generation sequencing and RNA sequencing, we characterised the HBV integration pattern in 45 HBV-associated B-cell NHL tumour tissues. RESULTS: A total of 354 HBV integration sites were identified in 13 (28.9%) samples, indicating the relatively low integration frequency in B-cell NHLs. High plasma HBV DNA loads were not associated with the existence of HBV integration. The insertion sites distributed randomly across all the lymphoma genome without any preferential hotspot neither at the chromosomal level nor at the genetic level. Intriguingly, most HBV integrations were nonclonal in B-cell NHLs, implying that they did not confer a survival advantage. Analysis of the paired diagnosis-relapse samples showed the unstable status of HBV integrations during disease progression. Furthermore, transcriptomic analysis revealed the limited biological impact of HBV integration. CONCLUSION: Our study provides an unbiased HBV integration map in B-cell NHLs, revealing the insignificant role of HBV DNA integration in B-cell lymphomagenesis.
RESUMO
In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), an endemic species that is used in Chinese medicine for its anti-tumor and immunomodulatory properties. In this study, we demonstrated that SY-1 profoundly decreased the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest (50-150 µM) and induction of apoptosis (>150 µM). Cell-cycle arrest induced by SY-1 was associated with a significant increase in levels of p53, p21/Cip1 and p27/Kip1, and a decrease in cyclins D1, D3 and A. In contrast, SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). The cells were cultured in soft agar to evaluate anchorage-independent colony formation, and we found that the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate for the first time that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. However, the detailed mechanisms of these processes remain unclear and will require further investigation.
RESUMO
A set of 10 4,7-dimethoxy-1,3-benzodioxole derivatives based on a lead compound previously discovered by our group, SY-1, which was isolated from Antrodia camphorata, were evaluated for their in vitro inhibitory activity on human colorectal carcinoma cells (COLO 205). Structure-activity relationship studies of the 10 compounds indicated the importance of the chain length of the alkyl group at the 5-position, and the 2-propenyl substituent named "apiole" exhibited the most potent inhibitory activity. In the present study, we demonstrate that the SY-1 analogue "apiole" decreased the proliferation of COLO 205 cells, but not that of normal human colonic epithelial cells (FHC). The G0/G1 cell cycle arrest induced by apiole (75-225 µM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, apiole (>150 µM) treatment significantly increased the levels of cleaved caspases 3, 8, 9 and bax/bcl-2 ratio and induced ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. These findings suggest that apiole can suppress COLO 205 cell growth; however, the detailed mechanisms of these processes require further investigation.
RESUMO
The purpose of this study was to analyse the major compound in the leaf essential oil of Cinnamomum osmophloeum Kaneh. and to examine its in vivo toxicity and cytokine-modulatory effects. The HS-GC/MS and quantitative HPLC analyses showed the concentrations of the major compounds, cinnamaldehyde, benzaldehyde and 3-phenylpropionaldehyde, in the leaf essential oil of Cinnamomum osmophloeum to be 16.88, 1.28 and 1.70 mg/mL, respectively. Acute and sub-acute toxicity tests identified no significant changes in body weight, liver and kidney function indices, and pathology for the mice treated with up to 1 mL/kg body weight of Cinnamomum osmophloeum leaf essential oil or up to 4 mg/kg body weight of cinnamaldehyde. A murine model was established using ovalbumin (OVA)-primed Balb/C mice treated with various concentrations of Cinnamomum osmophloeum leaf essential oil or cinnamaldehyde daily for 4 weeks. The results of tests with commercial ELISA kits indicated no significant cytokine-modulatory effects in mice treated with Cinnamomum osmophloeum leaf essential oil; however, the serum concentrations of IL-2, IL-4 and IL-10, but not IFN-γ, significantly increased in animals treated with 1 mg/kg body weight of cinnamaldehyde during the 4-week period. The possibility that the other constituents act as antagonists of cinnamaldehyde cannot be excluded.
Assuntos
Acroleína/análogos & derivados , Cinnamomum/química , Citocinas/sangue , Fatores Imunológicos/farmacologia , Óleos Voláteis/química , Extratos Vegetais/farmacologia , Acroleína/química , Acroleína/isolamento & purificação , Acroleína/farmacologia , Aldeídos/análise , Aldeídos/farmacologia , Animais , Benzaldeídos/análise , Benzaldeídos/farmacologia , Feminino , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Óleos Voláteis/isolamento & purificação , Ovalbumina , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
Although Rhodiola rosea (L.) is used widely and disseminated in Oriental medicine, its in vivo effects on cytokine modulation remain unclear. Among the biologically active components of Rhodiola rosea, salidroside was suggested to be the most active compound. The objectives of this study were to assess the toxicity and cytokine modulation effects of Rhodiola rosea standardised solution (RRSS) and salidroside. Quantitative high pressure liquid chromatography (HPLC) analysis determined the content of salidroside in RRSS to be 4.39% (w/v). Groups of Balb/c mice were fed daily with different doses of RRSS or salidroside, with CAPE or distilled water used as positive and negative controls, respectively. The acute and subacute toxicity tests did not reveal weight differences, pathological changes, or abnormalities in liver or kidney function indices among the treated groups. Ovalbumin-primed mouse cytokine assays demonstrated that both T helper (Th1) (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines were significantly increased by feeding with RRSS in a dose- and time-dependent manner (p < 0.05). Moreover, the cytokine modulation effects of salidroside were less prominent than that of RRSS treatment and not dose-dependent. These findings suggest that increased secretion of both Th1- and Th2-pattern cytokines can be achieved with RRSS and salidroside treatment.
Assuntos
Citocinas/metabolismo , Glucosídeos/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Rhodiola/química , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta Imunológica , Feminino , Glucosídeos/análise , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fenóis/análise , Extratos Vegetais/análise , Baço/citologia , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2-3% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.
Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Antivirais/administração & dosagem , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Polimerase Dependente de RNA/antagonistas & inibidores , RNA Polimerase Dependente de RNA/genética , Taiwan , Falha de Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genéticaRESUMO
Berberine is an alkaloid extracted from Coptidis rhizome. Among the individual herbal components of a Chinese herb medicine, Ching-Wei-San, Coptidis Rhizoma has the most potent antimicrobial activity. By high-pressure liquid chromatography, the quantitative analysis of berberine from 6.25-mg/mL (w/v) Coptidis rhizome extract or 50.00-mg/mL (w/v) Ching-Wei-San was determined to be 0.26 mg/mL. To explore the potential use of Ching-Wei-San against herpes simplex virus (HSV) infection, the cytotoxicity, anti-HSV-1 and anti-HSV-2 activity in Vero cells were assayed. The selectivity index of berberine was about 1.2-1.5 times higher than that of Coptidis rhizome extract and Ching-Wei-San. Moreover, the antiviral activities correspond to the content of berberine in the aqueous solution. Berberine may interfere with the viral replication cycle after virus penetration and no later than the viral DNA synthesis step, and its activities were not affected by the preparation processes. Berberine, the natural plants that contain this component, including Coptidis rhizome, and Ching-Wei-San have all shown anti-HSV effects.
Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Plantas Medicinais/química , Simplexvirus/efeitos dos fármacos , Animais , Antivirais/análise , Antivirais/isolamento & purificação , Antivirais/toxicidade , Berberina/análise , Berberina/isolamento & purificação , Berberina/toxicidade , Chlorocebus aethiops , Cromatografia Líquida de Alta Pressão , Coptis chinensis , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Liver cirrhosis is an uncommon but not rare side effect of amiodarone-induced hepatotoxicity. Patients with hepatitis B virus and hepatitis C virus infections are at a high risk for developing liver cirrhosis. However, the relationship between this treatment and risk of liver cirrhosis in high-risk chronic hepatitis B and chronic hepatitis C patients is unknown. PATIENTS AND METHODS: The present study identified amiodarone users (N=8,081) from the Taiwan National Health Insurance Research Database from 1997 through 2013. A total of 32,324 subjects with age, comorbidities, gender, and index date-matched non-amiodarone users were selected as controls (non-amiodarone cohort). The incidences of cumulative liver cirrhosis were compared between cohorts. Stratified Cox's regression hazard models were used to assess possible comorbidity-attributable risks for liver cirrhosis. RESULTS: The amiodarone cohort had a nonsignificant risk of liver cirrhosis compared with the non-amiodarone cohort, with a HR of 1.17 (95% CI: 0.93-1.47; P=0.1723). Patients with specific comorbid diseases, including type 2 diabetes mellitus, chronic hepatitis B, chronic hepatitis C, and heart failure, were probably at a high risk of developing liver cirrhosis. The use of statins was associated with a significant 42% reduction in the risk of liver cirrhosis. CONCLUSION: Patients in the amiodarone cohort had no excess risk of liver cirrhosis compared with patients in the non-amiodarone cohort. Long-term surveillance for liver toxicity in high-risk patients with amiodarone treatment is suggested.
RESUMO
A 2-phenyl-4-quinolone (2-PQ) derivative, 2-(3-fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1), was synthesized in our laboratory. In this study, we delineated the growth-inhibitory effect of YJC-1 in human lung carcinoma A549 cells. YJC-1 inhibited cell growth with an IC(50) value of about 4.8 microM via microtubule polymerization, causing growth arrest in the mitotic phase. Immunoblotting analysis revealed a dramatic induction of cyclin-dependent kinase (CDK) inhibitor p21(Cip1/Waf1) and down-regulation of Cdc25C phosphatase to inhibit the protein expression of cyclin B1 and CDK1. We also found that YJC-1 induced a profound time-dependent elevation in p21(Cip1/Waf1) gene expression in comparison with the negative control. In vivo, we also found that YJC-1 significantly suppressed tumor growth in mice inoculated with A549 cells. These findings suggest that YJC-1 can suppress A549 cell growth via mitotic phase arrest.
Assuntos
Antimitóticos , Mitose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Citometria de Fluxo , Humanos , Microscopia de Fluorescência , Microtúbulos/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Ferulic acid is one of the most ubiquitous phenolic compounds in nature, which has antioxidant and anticancer activities. However, ferulic acid derivatives, such as ferulamide have never been reported. MATERIALS AND METHODS: (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide (compound 8), a ferulamide derivative was synthesized in our laboratory. In this study, HL-60 cells were treated with various concentrations of compound 8, and its effects on cell growth, cell cycle, apoptosis and related measurements were investigated. RESULTS: Compound 8 inhibited cell growth in a concentration- and time-dependent manner with significant cytotoxicity, and the concentration required to inhibit growth by 50% (IC50) was 8.2 microM for 24 h. The cell cycle analysis indicated that compound 8 treated cells were arrested in the G2/M-phase and followed by apoptosis. Microscopic examination showed that treatment with compound 8 displayed typical morphological features of apoptotic cells, with cell shrinking and formation of apoptotic bodies. Reverse transcription-polymerase chain reaction (RT- PCR) analysis showed a dramatic induction of CDK inhibitor p21, which inhibited the expression of cyclin B1, thereby resulting in G2/M phase arrest. After G2/M-phase arrest, cells underwent apoptosis via significant down-regulation of Bcl-2 expression. CONCLUSION: These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects.
Assuntos
Acrilamidas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Acrilamidas/química , Antineoplásicos/química , Ciclo Celular/genética , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Genes bcl-2/efeitos dos fármacos , Células HL-60 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genéticaRESUMO
OBJECTIVES: To investigate whether three strains of probiotics, L. acidophilus, L. rhamnosus, and L. sporogenes, had signifificant inhibitive effects on Helicobacter pylori (H. pylori). METHODS: This is a 4-week, randomly assigned, parallel-group, doubled-blind, and placebo-controlled study. Fifty patients with a positive H. pylori infection urea breath test (â³UBT) result > 10% and without ulcer symptoms were randomized into a treatment group and a placebo group by a computer generated allocation sheet with 1:1. These subjects took one capsule of probiotics or placebo twice daily. The primary measurement was the change in â³UBT values. RESULTS: The â³UBT values during the 4-week treatment period and the 2-week follow-up period were not signifificantly different between the treatment group and the placebo group, indicating that the inhibitive effects on H. pylori were comparable between both groups. The monocyte count (%) was 5.77±1.11 in the treatment group versus 5.09±1.12 in the placebo group (P=0.044), and the basophile count was 0.55±0.32 in the treatment group versus 0.36±0.23 in the placebo group (P=0.024) at week 2 of the treatment period, both of which reached statistical signifificance. The monocyte count was 5.75±1.26 in the treatment group and 4.72±0.99 in the placebo group at the end of the follow-up period (P=0.003). CONCLUSION: There was no signifificant inhibitive effects of the three probiotic strains (L. acidophilus, L. rhamnosus, and L. sporogenes) on H. pylori. Probiotics can not play the same role as antibiotics in the eradication of H. pylori, the role of probiotics is likely to be important as adjuvant to the triple or quadruple therapy for H. pylori, especially in resistance cases.
Assuntos
Helicobacter pylori/efeitos dos fármacos , Lactobacillus/metabolismo , Probióticos/farmacologia , Adulto , Idoso , Testes Respiratórios , Demografia , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/administração & dosagem , Probióticos/efeitos adversos , Ureia/análise , Adulto JovemRESUMO
OBJECTIVE: To observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies. METHODS: A double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8. RESULTS: At week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride. CONCLUSION: The combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.
Assuntos
Produtos Biológicos/uso terapêutico , Colesterol/sangue , Hiperlipidemias/sangue , Hiperlipidemias/terapia , Hipolipemiantes/uso terapêutico , Lacticaseibacillus casei/fisiologia , Produtos Biológicos/efeitos adversos , Produtos Biológicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Terapia Combinada , Demografia , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Hiperlipidemias/fisiopatologia , Hipolipemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
1-(3,4-dimethoxyphenyl)-3,5-dodecenedione (I6), a gingerdione derivative, was synthesized in our laboratory, has been demonstrated to be an effective anti-tumor agent in human leukemia cells. Gingerdione is one of the components from ginger. In the present study, we found that I6 could inhibit cell proliferation in the time- and dose-dependent manner in human promyelocytic leukemia HL-60 cells. To investigate the anti-proliferation mechanism of I6, cell cycle analysis was performed. Results showed that I6 induced significant G1 arrest and apoptosis in HL-60 cells. It was proved by the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of regulatory on G1 arrest that the levels of p15 and p27 increased after treatment and mRNA levels of cyclin D2, cyclin E, and cdc25A were decreased. The I6-induced apoptosis was further confirmed by DNA fragmentation assay. The DNA gel electrophoresis showed that I6 induced DNA fragmentation, a biochemical hallmark of apoptosis, in HL-60 cells. I6-induced apoptosis was accompanied by an apparent up-regulation of caspase-3, and down-regulation of Bcl-2. Taken together, these results suggest that markedly down-regulation of G1 associated cyclin D2, cyclin E and cdc25A and up-regulation of CDKI, p15 and p27, and may contribute to I6-mediated cell cycle arrest. Furthermore, the Bcl-2 expression decrease and caspase-3 activation may be the plausible mechanism by which I6 induced apoptosis. These results suggest that I6 is a potent anti-HL-60 drug and possess a significant action on cell cycle before commitment for apoptosis occurrence.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Antineoplásicos/química , Caspase 3 , Caspases/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Zingiber officinale/química , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/patologia , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/análiseRESUMO
Antrodia camphorata (A. camphorata) is a unique, endemic and extremely rare mushroom species native to Taiwan, and both crude extracts of and purified chemical compounds from A. camphorata have been reported to have a variety of significant beneficial effects, such as anti-tumor and anti-inflammatory activity. However, reports on the effects of A. camphorata against dental pathogens have been limited. Oral health is now recognized as important for overall general health, including conditions such as dental caries, periodontal disease and rheumatoid arthritis. Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) are the most common bacteria associated with dental plaque and periodontopathic diseases, respectively. Thus, our study examined the ability of five various crude extracts of A. camphorata to inhibit the growth of dental bacteria and anti-adherence in vitro. Among the extracts, the ethanol, ethyl acetate and chloroform extracts exhibited the lowest MICs against P. gingivalis and S. mutans (MICâ=â4â¼16 µg/mL). The MIC of the aqueous extract was greater than 2048 µg/mL against both P. gingivalis and S. mutans. In vitro adherence of S. mutans was significantly inhibited by the addition of either the ethyl acetate extract or chloroform extract (MICâ=â16â¼24 µg/mL), while the ethanol extract (MICâ=â32â¼64 µg/mL) exhibited moderate inhibitory activity. Based on the result of this study, the ethyl acetate and chloroform extracts of A. camphorata may be good candidates for oral hygiene agents to control dental caries and periodontopathic conditions.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antrodia/química , Bactérias/efeitos dos fármacos , Cárie Dentária/microbiologia , Testes de Sensibilidade Microbiana , Porphyromonas gingivalis/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacosRESUMO
As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-phenyl group displayed the highest in vitro anticancer activity. Activity decreased significantly if a chlorine or methoxy group replaced the fluorine atom. 3'-Fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (68) had the highest in vitro cytotoxic activity among all tested carboxylic acid derivatives and their salts. The mechanism of action may be similar, but not identical, to that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits further investigation as a novel hydrophilic antimitotic agent.