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1.
Arch Rheumatol ; 37(2): 261-270, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36017203

RESUMO

Objectives: This study aims to investigate the association of serum lysyl oxidase (LOX) levels with systemic sclerosis (SSc), to examine the relationship between LOX and disease onset, and to evaluate the probable effects of hyperlipidemia on the circulating levels of LOX among patients with SSc. Patients and methods: Between May 2017 and November 2018, a total of 39 patients with SSc (2 males, 37 females; mean age: 46.6±12.3 years; range, 18 to 65 years) and 35 healthy controls (4 males, 31 females; mean age: 43.1±14.1 years; range, 18 to 65 years) were included. Serum LOX concentration was measured using the enzyme-linked immunoassay in triplicate. Results: We found higher levels of serum LOX in patients with SSc compared to healthy controls. There was a significant relationship between serum LOX levels and disease onset. Patients with long-standing disease demonstrated increased levels of LOX in the blood compared to the recent-onset group. Hyperlipidemia did not have a significant effect on circulating levels of LOX. There was a significant negative correlation between LOX levels and modified Rodnan Skin Score in the subgroup of patients with skin involvement only and in patients without gastrointestinal involvement. Conclusion: Our study findings show an increased level of LOX protein level in the blood of patients diagnosed with SSc. Hyperlipidemia seems not to affect the concentrations of LOX in the peripheral blood of patients with SSc.

2.
Adv Respir Med ; 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35084728

RESUMO

INTRODUCTION: Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppressive effects in previous studies. In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. RESULTS: The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10⁻7M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. CONCLUSION: In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction.

3.
Middle East J Dig Dis ; 13(2): 115-120, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34712449

RESUMO

BACKGROUND Pancreatic cancer is considered as the most deadly tumor among gastrointestinal cancers because of its poor prognosis. The frequently deregulated pathway in the cancer cell is associated with an increased expression of various genes, including the synthesis of fatty acids. We aimed to evaluate the level of serum fatty acid synthase (FASN) as a diagnostic marker for early diagnosis of pancreatic cancer. METHODS Serum FASN levels were measured by ELISA in 92 patients with pancreatic adenocarcinomas and in 92 healthy controls. Logistic regression analysis was used to identify independent predictors of certain diagnostic categories. RESULTS Serum FASN levels were significantly higher in patients with pancreatic cancer than in healthy controls (1.35 [0.98-2.3] ng/mL vs 1.04 [0.19-1.34] ng/mL, p < 0.001) and in smokers compared to non-smokers (1.41 [0.79-2.52] ng/mL vs 1.07 [0.21-1.74] ng/mL, p < 0.001). FASN levels and smoking were associated with increased risk of PC (1.54 [1.1- 2.14] ng/mL, p = 0.011 and 5.69 [2.68-12.09] ng/mL, p < 0.001, respectively). CONCLUSION Elevated serum FASN levels in patients with pancreatic cancer indicate the need for the production of large numbers of lipids for the survival and proliferation of human cancer cells and the diagnostic value of FASN as a new diagnostic biomarker.

5.
Mediterr J Hematol Infect Dis ; 13(1): e2021049, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276918

RESUMO

BACKGROUND: As a major carotenoid in saffron, crocin demonstrates potent anti-cancer impacts. However, its anti-lymphoma effects remain vague, especially in the human EBV-associated B-cell lymphoproliferative disorders. This study examined crocin's apoptogenic potential and its underlying mechanism in CO 88BV59-1 cell line vs. normal human peripheral blood B cells. METHODS: CO 88BV59-1 cells were treated with crocin alone or in combination with vincristine for up to 72 h. The cell viability was examined using a resazurin assay. Flow cytometry using annexin V and propidium iodide labeling was performed to detect apoptotic cells. Also, the expression levels of genes and proteins involved in apoptosis (CASP3, CASP8, CASP9, P53, Bax, and Bcl-2) were respectively determined via real-time PCR and Western blot analysis. RESULTS: Crocin concentration-dependently reduced cell viability in CO 88BV59-1 cells with no significant toxicity toward normal B cells. Similar to vincristine, crocin significantly increased apoptosis in these cells during 72 h of incubation. Furthermore, the combination of crocin (80 µM) and vincristine (1 µM) enhanced apoptosis in CO 88BV59-1 cells. Therefore, this synergistic effect was detected in human EBV-transformed B-lymphocyte. CASP3, CASP9, P53, and Bax/Bcl-2 ratio expressions were significantly raised in CO 88BV59-1 cells, whereas CASP8 was unaltered. It was proposed that crocin promoted apoptosis in CO 88BV59-1 cells in a time- and concentration-dependent manner via the induction of the intrinsic pathway. CONCLUSION: The results suggest that crocin may serve as a good alternative/coadjuvant to vincristine in EBV-associated B-cell lymphoproliferative disorders.

6.
Avicenna J Phytomed ; 11(4): 314-323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290963

RESUMO

OBJECTIVE: Acute promyelocytic leukemia (APL) is among the most threatening hematological malignant cancers. Defects in cell growth and apoptotic pathways lead to the pathogenesis of the disease as well as its resistance to therapy; therefore, it is a good model for examining pro-apoptotic agents. The present study compared the molecular mechanism induced by kaempferol and epigallocatechin gallate (EGCG) as well as all-trans retinoic acid (ATRA), in HL-60 leukemia cells during five days. MATERIALS AND METHODS: Cell viability was determined by resazurin assay following treatment with ATRA (10 µM), EGCG, and kaempferol (12.5-100 µM), and apoptosis was detected by the ANX V/PI kit. Moreover, the levels of genes involved in apoptosis (PI3K, AKT, BCL2, BAX, P21, PTEN, CASP3, CASP8, and CASP9) and multi-drug resistance (MDR, ABCB1 and ABCC1) were assessed by using real-time PCR test. RESULTS: Based on the findings, kaempferol decreased cell viability and increased apoptosis in HL60 cells more than EGCG. Apoptosis was induced via extrinsic and intrinsic pathways in HL60 cells by kaempferol and EGCG. In addition, kaempferol and EGCG increased apoptosis and inhibited MDR in a concentration- and time-dependent manner. CONCLUSION: Kaempferol at high concentrations can be taken into consideration for treating patients with APL as compared with EGCG.

7.
Clin Rheumatol ; 40(10): 3897-3918, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33796953

RESUMO

The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab's safety and efficacy profile in SSc patients. A systematic online query was performed in PubMed, Scopus, Web of Science, and Embase. The studies on the application of rituximab for patients with SSc were reviewed comprehensively for over two years. In terms of efficacy profile, mRSS, MS, LVEF, sPAP, FVC, DLCO, TLC, FEV, DAS, severity activity, HAQ-DI and SF36 were assessed for organ involvement and quality of life. The level of biological and immunological markers was also evaluated in SSc patients treated with RTX. In total, 24 studies met the criteria. Although they did not have a high quality, they were free from heterogeneity and publication bias. The pooled results revealed a long-term improvement in mRSS and MS. HAQ-DI was improved to 0.78 after 12 months, and DAS was significantly reduced to 0.33, 0.23, and 0.24 following 6, 12, and 24 months of treatment, respectively (p = 0.00 for both parameters). The rest of the parameters remained stable over time in patients with SSc. The pooled analysis of these patients demonstrated that the induction of death, cancer, infection, and infusion were 9, 5, 18 and 10%, respectively. Based on the pooled results of this meta-analysis, rituximab improves skin score and disease indices and stabilizes organ involvement in SSc patients. Rituximab seems to possess reasonable safety, similar to previous data from other autoimmune diseases.


Assuntos
Esclerodermia Localizada , Escleroderma Sistêmico , Humanos , Qualidade de Vida , Rituximab/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Pele
8.
Tanaffos ; 20(2): 116-125, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34976082

RESUMO

BACKGROUND: This study aimed to determine the prevalence of sleep apnea and its associated factors in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: This population-based cross-sectional study included 47 CKD patients, referred to the dialysis unit of Kosar Hospital in Semnan, Iran, in 2017. Two questionnaires were used for data collection. The first questionnaire included demographic and clinical variables, and the second questionnaire (STOP-BANG questionnaire) was used to measure sleep apnea in CKD patients. Also, the Apnea-Hypopnea Index (AHI) was calculated for all patients and was considered as the gold standard. To determine the factors associated with sleep apnea, univariate and multiple logistic regression models were used. Finally, the area under the receiver operating characteristic curve (ROC) was determined for assessing the discriminative ability of the model, as well as the accuracy of STOP-BANG questionnaire. STATA version 14 was used for data analysis. RESULTS: The prevalence of sleep apnea in CKD patients was 53.2%. Also, its prevalence in women and men was 52% and 48%, respectively. In the multiple logistic regression model, body mass index (BMI) (OR: 1.21, 95% CI: 1.04-1.31) and blood urea nitrogen (BUN) (OR: 0.94, 95% CI: 0.91-0.98) had significant associations with sleep apnea in CKD patients; the area under the ROC curve was 0.7982 for this model. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve of STOP-BANG questionnaire for AHI≥15 were 71.43, 61.54, 60, 72.73, and 0.6932, respectively. CONCLUSION: This study showed that the prevalence of sleep apnea in CKD patients was high. Given the acceptable validity of STOP-BANG questionnaire, this scale can be used to screen sleep apnea in CKD patients.

9.
J Immunoassay Immunochem ; 41(4): 768-777, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32397924

RESUMO

Inflammation is a common feature of type 2 diabetes (T2D). Inflammatory cytokines increase in patients with type 2 diabetes, metabolic syndrome, and heart disease. Various types of cells can produce inflammatory cytokines and then release them into the bloodstream, where their complex interactions with target tissues raise a tissue-specific immune response. This review focused on C-reactive protein (CRP), tumor necrosis factor (TNF)-α as an inflammatory cytokine, and adiponectin produced by adipose tissues. Despite the major role of cytokines in the development of T2D, further studies are required to investigate the possible effects of the macronutrient composition of diet on these cytokines.


Assuntos
Citocinas/biossíntese , Diabetes Mellitus Tipo 2/imunologia , Dieta/efeitos adversos , Inflamação/imunologia , Adiponectina/biossíntese , Animais , Proteína C-Reativa/biossíntese , Humanos , Fator de Necrose Tumoral alfa/biossíntese
10.
Middle East J Dig Dis ; 11(1): 5-16, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31049177

RESUMO

Therapeutic targeting of phosphatidyl-inositol 3-kinase (PI3K) is considered as a possible strategy in several types of cancer, including gastrointestinal ones. In vitro and in vivo studies indicated the significance of proapoptotic and antiproliferative inhibition of PI3K. Although there are many phase 1 and 2 clinical trials on PI3K inhibitors in patients with gastrointestinal cancer, the molecular mechanism of PI3K targeting PI3K/ mTOR pathway is not clear. Panclass I, isoformselective, and dual PI3K/mTOR inhibitors are under investigation. This review aimed to indicate PI3K-dependent targeting mechanisms in gastrointestinal cancer and the evaluation of related clinical data.

11.
Middle East J Dig Dis ; 11(1): 38-44, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31049181

RESUMO

BACKGROUND Aryl-carbon receptor (AhR), a ligand-activated transcription factor, is best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. AhR is expressed in several tumor cells and regulates the expression of genes in the signal transduction pathways. In this study, we examined the soluble levels of AhR in patients with pancreatic cancer. METHODS 123 samples, including 59 (48%) samples of pancreatic ductal adenocarcinoma based on histological evidence and 64 (52%) healthy control samples, were evaluated to determine plasma levels of AhR by Enzyme-linked immunoassay. RESULTS The median of AhR among patients was 0.280 ng/mL, which differed considerably from 0.07 ng/mL in the control group (p < 0.001). Significant differences of the AhR were observed between the plasma samples of the patients compared with the healthy group, with respect to male sex (p < 0.001), age groups (p = 0.001), diabetic status (p < 0.001), body mass index (BMI) categories (p = 0.035), and constantly smokers (p < 0.001). We also observed significant differences between the level of AhR expression between men and women (p = 0.01) and ever to never smokers (p = 0.009) in the case group. In addition, the age of 65 and a BMI of 25 or less were significant factors in plasma AhR levels ([1.61 95%CI 1.08-2.38] and [1.84 95%CI 1.22-2.77], respectively). CONCLUSION The results of this study can add diagnostic information to pancreatic cancer involving AhR and the potential efficacy of this receptor in therapeutic strategies.

12.
J Cell Biochem ; 120(4): 4732-4738, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30644127

RESUMO

Saffron (Crocus sativus L.), and its main constituents, crocin, and crocetin have shown promising effects as an antileukemic agent in animal models and cell culture systems. Saffron retards the growth of cancer cells via inhibiting nucleic acid synthesis and enhancing antioxidative system. It can induce apoptosis and chemosensitivity via inhibiting multidrug resistance proteins. Saffron also induces differentiation pathways via inhibiting promyelocytic leukemia/retinoic acid receptor-α, histone deacetylase1, and tyrosyl DNA phosphodiesterase-1 as well. The present review highlights the most recent findings on the antileukemic effects of saffron and its underlying molecular targets. The emerging evidence suggests that saffron has a selective toxicity effect against leukemic cells while is safe for the normal cells.


Assuntos
Antineoplásicos/farmacologia , Carotenoides/farmacologia , Crocus/química , Leucemia/tratamento farmacológico , Animais , Carotenoides/química , Carotenoides/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Leucemia/patologia , Leucemia/prevenção & controle , Terapia de Alvo Molecular , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Cell Biochem ; 120(2): 1943-1957, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30203596

RESUMO

Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects. However, the antileukemic effects of crocetin are still unclear, especially in primary acute promyelocytic leukemia (APL) cells. In the current study, the potential antipromyelocytic leukemia activity of crocetin and the underlying molecular mechanisms were investigated. Crocetin (100 µM), like standard anti-APL drugs, all-trans retinoic acid (ATRA, 10 µM) and As2 O 3 (arsenic trioxide, 50 µM), significantly inhibited proliferation and induced apoptosis in primary APL cells, as well as NB4 and HL60 cells. The effect was associated with the decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl-DNA phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes CASP3, CASP9, and BAX/BCL2 ratio were significantly increased. In contrast, crocetin at relatively low concentration (10 µM), like ATRA (1 µM) and As 2 O 3 (0.5 µM), induced differentiation of leukemic cells toward granulocytic pattern, and increased the number of differentiated cells expressing CD11b and CD14, while the number of the immature cells expressing CD34 or CD33 was decreased. Furthermore, crocetin suppressed the expression of clinical marker promyelocytic leukemia/retinoic acid receptor-α ( PML/RARα) in NB4 and primary APL cells, and reduced the expression of histone deacetylase 1 ( HDAC1) in all leukemic cells. The results suggested that crocetin can be considered as a candidate for future preclinical and clinical trials of complementary APL treatment.

14.
Avicenna J Phytomed ; 8(3): 237-245, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29881709

RESUMO

OBJECTIVE: Cuscuta campestris or common dodder is a holoparasitic plant that has been valorized for treatment of liver injury and cancer prevention in traditional medicine. Recently, extract of C. campestris had shown moderate antimicrobial properties and cytotoxic effects. In this study, we examined the level of cellular oxidants, cytotoxicity, apoptosis and differentiation induced by hydroalcoholic extract of C. campestris (CCE) (12.5-200 µg/ml), as well as arsenic trioxide (As2O3, 50 µM), in human leukemic (HL60 and NB4) and normal polymorph nuclear cells after 72 hr treatment. MATERIALS AND METHODS: Resazurin assay was used to determine cell viability following treatment with C. campestris. Intracellular reactive oxygen species (ROS) and apoptotic cells were measured by fluorimetry using carboxy 2', 7'-dichlorofluorescein diacetate and propidium iodide (PI), as staining reagents, respectively. The differentiation of leukemic cells was evaluated by Giemsa staining and nitro blue tetrazolium (NBT) reduction. RESULTS: C. campestris inhibited cell viability with IC50 values of 23.9 µg/ml for HL60 and 60.3 µg/ml for NB4 cells after 72 hr treatment. ROS formation was also concentration-dependently increased following treatment with C. campestris. In addition, the number of apoptotic cells significantly increased to 88.4% and 62.3% in CCE (200 µg/ml)-treated HL60 and NB4 cells, respectively, which was higher than that of As2O3 (50 µM)-treated leukemic cells (p<0.001). Nonetheless, C. campestris did not induce differentiation of leukemic cells towards granulocytic pattern. CONCLUSION: The present study demonstrated that C. campestris induced apoptosis through ROS production without having differential effect on leukemic cells, in concentration- and time-dependent manners. Understanding of precise signaling pathway by which C. campestris induce apoptosis, needs further research.

15.
J Cell Biochem ; 119(2): 2288-2297, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28865123

RESUMO

Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 µM) and all-trans retinoic acid (ATRA; 10 µM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients.


Assuntos
Quempferóis/farmacologia , Leucemia Promielocítica Aguda/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes MDR/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico
16.
Phytother Res ; 32(3): 471-479, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29193405

RESUMO

The use of all-trans retinoic acid (ATRA) has dramatically improved the treatment and survival rate of patients with acute promyelocytic leukemia (APL). However, toxicity and resistance to this drug are major problems in the treatment of APL with ATRA. Earlier studies have suggested that the green tea polyphenol epigallocatechin gallate (EGCG) induces cell death in hematopoietic neoplasms without adversely affecting normal cells. In the present study, the potential therapeutic effect of EGCG in APL and the underlying molecular mechanisms were investigated. EGCG (100 µM) significantly inhibited proliferation and induced apoptosis in HL-60 and NB4 cells. This effect was associated with decreased expressions of multidrug resistance proteins ABCB1, and ABCC1, whereas the expressions of pro-apoptotic genes CASP3, CASP8, p21, and Bax/Bcl-2 ratio were significantly increased. EGCG, at 25 µM concentration, induced differentiation of leukemic cells towards granulocytic pattern in a similar manner to that observed for ATRA (1 µM). Furthermore, EGCG suppressed the expression of clinical marker PML/RARα in NB4 cells and reduced the expression of HDAC1 in leukemic cells. In conclusion, the results suggested that EGCG can be considered as a potential treatment for APL.


Assuntos
Catequina/análogos & derivados , Histona Desacetilase 1/metabolismo , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/metabolismo , Apoptose , Catequina/metabolismo , Diferenciação Celular , Proliferação de Células , Humanos , Leucemia Promielocítica Aguda/patologia
17.
J Cell Physiol ; 233(3): 2170-2182, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28407293

RESUMO

Natural products have gained a wide popularity as chemopreventive and anti-cancer agents owing to their multi-mechanistic mode of action, availability and synergism with several conventional chemotherapeutic agents. Crocetin is a carotenoid compound isolated from the stigma of Crocus sativus L. (saffron). Crocetin has shown promising effects as an anti-tumor agent in animal models and cell culture systems. Crocetin retards the growth of cancer cells via inhibiting nucleic acid synthesis, enhancing anti-oxidative system, and inducing apoptosis and differentiation pathways. The present review outlines natural sources of crocetin, and its pharmacokinetic and pharmacological properties relevant to the prevention and treatment of cancer. Also, we discuss molecular targets underlying the putative anti-tumor effects of crocetin.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos/farmacologia , Carotenoides/farmacologia , Quimioprevenção/métodos , Neoplasias/tratamento farmacológico , Inibidores da Síntese de Ácido Nucleico/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Crocus/química , Humanos , Neoplasias/prevenção & controle , Vitamina A/análogos & derivados
18.
Folia Neuropathol ; 56(4): 354-361, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30786673

RESUMO

Glutamate is considered to be responsible for the pathogenesis of many neurodegenerative diseases. Reactive oxygen species (ROS) production is considered to be involved in the glutamate-induced apoptosis process. In this study, we investigated the neuroprotective effects of Rheum turkestanicum in the glutamate-induced rat pheochromocytoma (PC12 cells) and mouse neuroblastoma (N2a) cell lines. Rutin as an antioxidant was used as positive control. Glutamate cytotoxicity was accompanied by an increment of malondialdehyde (MDA) content, ROS generation and apoptosis induction. However, pretreatment with the root extract of R. turkestanicum significantly reduced MDA content, ROS generation and apoptotic cell death. Also rutin at a dose of 100 µM reduced ROS production and protected against glutamate toxicity. Also the quantification of rutin in R. turkestanicum extract was achieved and was about 0.11% ± 0.01 w/w. All these findings indicated that R. turkestanicum protected PC12 and N2a cells against glutamate-induced oxidative cell death and apoptosis and might raise the possibility of R. turkestanicum usage as a neuroprotective agent.


Assuntos
Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Rheum
19.
Cell Mol Biol (Noisy-le-grand) ; 63(11): 17-22, 2017 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-29208170

RESUMO

Ferula species known for its oleo-resins that are recognized valuable industrial crops and food products. In this study, we examined the level of cellular oxidants, cytotoxicity, apoptosis and differentiation induced by oleo resin gum from Ferula gummosa (30-250 µg/mL), as well as Arsenic trioxide (50 µM, as positive control), in leukemic (NB4 and HL-60 cells) and normal polymorph nuclear cells during 72 h. Resazurin assay was used to determine cell viability following treatment with F. gummosa (30-250 µg/mL). Intracellular reactive oxygen species was measured by fluorimetry using carboxy 2', 7'-dichlorofluorescein diacetate. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Differentiation of cells evaluated by Giemsa staining and Nitro Blue Tetrazolium reduction. F. gummosa showed a concentration-dependent suppression in cell survival with IC50 values of 41.8 µg/mL for HL60 and 59.2 µg/mL for NB4 cells after 72 h treatment. ROS formation and apoptotic cells were concentration-dependently increased following treatment with F. gummosa, similar to As2O3. F. gummosa did not induce differentiation of leukemic cells towards granulocytic pattern. The resin did not have toxic effect on PMN cells (<800 µg/mL). In conclusion, the present study demonstrated that F. gummosa induced apoptosis through ROS mechanism on leukemic cells as a concentration and time dependent manner. The precise signaling pathway by which F. gummosa induce apoptosis needs further research.


Assuntos
Apoptose/fisiologia , Ferula/química , Leucemia/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células Cultivadas , Células HL-60 , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
20.
Pharmacol Rep ; 69(5): 924-928, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28646740

RESUMO

BACKGROUND: Green tea has antioxidant, anti-tumor and anti-bacterial properties. Epigallocatechin-3-gallate (EGCG) in green tea is highly active as a cancer chemopreventive agent. In this study, we designed a series of experiments to examine the effects of EGCG on proliferation and apoptosis of estrogen receptor α-positive breast cancer (T47D) cells. METHODS: Cells were treated with EGCG (0-80µM) and tamoxifen (0-20µM), as the positive control, up to 72h. Cell viability was determined by MTT assay. Apoptosis investigated by real time PCR of apoptosis and survival (Bax, Bcl-2, p21, p53, PTEN, PI3K, AKT, caspase3 and caspase9 and hTERT) genes and by western blot of Bax/Bcl-2 proteins expressions. RESULTS: The results showed that EGCG decreased cell viability as concentration- and time-dependently. IC50 values were 14.17µM for T47D and 193.10µM for HFF cells, as compared with 3.39µM and 32.75µM for tamoxifen after 72h treatment, respectively. Also, EGCG (80µM) significantly increased the genes of PTEN, CASP3, CASP9 and decreased AKT approximately equal to tamoxifen. In gene expression, EGCG (80µM) significantly increased Bax/Bcl-2 ratio to 8-fold vise 15-fold in tamoxifen (20µM)-treated T47D cells during 72h. In protein expression of Bax/Bcl-2, EGCG significantly increased 6-fold while this ratio augmented 10-fold in tamoxifen group. EGCG significantly decreased 0.8, 0.4 and 0.3 gene expression of hTERT in 24, 48 and 72h, respectively. CONCLUSIONS: This study suggests that EGCG may be a useful adjuvant therapeutic agent for the treatment of breast cancer.


Assuntos
Catequina/análogos & derivados , Regulação para Baixo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Telomerase/metabolismo , Antioxidantes/farmacologia , Apoptose , Neoplasias da Mama , Catequina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Telomerase/genética
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