The effects of hesperetin on apoptosis induction andinhibition of cell proliferation in the prostate cancer PC3 cells

ntroduction: Prostate cancer is the second leading cause of cancer-related deaths and the mostcommon cancer diagnosed in men in the United States and Europe. Hesperetin, a member of thef lavonoids with antioxidant property, is found in fruits such as oranges and red fruits. This study was undertaken to evaluate the effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells.Methods: PC3 cell line was cultured in standard condition. The cells were exposed to differentconcentrations of hesperetin (0-1000 μM) for 48 hours. Cell viability was measured by MTT assay.Apoptosis induction was assessed by Annexin V-FITC by flow cytometry analysis.Results: The PC3 cells exposed to hesperetin (0-1000 μM) exhibited an IC (inhibitoryconcentration of 50) about 450 μM. At different concentrations of hesperetin (400, 450 and 500µm), the apoptosis increased slightly (not significant) in treated PC3 cells compared to the controlgroup (5.4, 7.8 and 9.1 respectively vs. 4.2).Conclusion: These results clearly show that hesperetin can lead to inhibition of PC3 cellsproliferation.&nbsp

Alteration of T cell subtypes in beta-thalassaemia major: Impact of ferritin level

Introduction: Oxidative damage and regular antigenic stimulation are main factors in accelerating immunosenescence. The present study was conducted to investigate new concepts of early immunosenescence in thalassaemia patients. aterials and Methods: Twenty seven beta-thalassaemia major patients and a group of matched healthy volunteers aged 10-30 years in Shahrekord, Iran were recruited into the study. Ferritin level was determined and CD4 or CD8 T cells were analysed versus phenotyping markers, CD27, CD28, CD57 and CCR7, by flowcytometry. Data were analysed by Mann-Whitney and Spearman’s correlation coefficient test in SPSS 11.5. Results: Absolute lymphocytosis and partial decrease in T cells were observed in the patients. CD4+CD57+ and CD4+CCR7- T cells were significantly higher, whereas CD8+CD27+ and CD8+CCR7+ T cells were partially higher in patients. A negative correlation was observed between ferritin level and number of CD8+CD27+ and CD8+CCR7+ T cells, whereas the correlation was positive between ferritin level and number of CD57+ T cells. Conclusion: Moderate alteration of T cell repertoire and increase in CCR27-, CCR7-, and CD57+ T cells could reflect antigenic stimulation, decline in naïve T cells, and being closer to terminally differentiated cells. Effect of iron overload is potentially explained by positive correlation of blood transfusion and ferritin level with frequency of CD3+CD27- and that of ferritin with frequency of CD57+ T cells

Gallic Acid Inhibits Proliferation and Induces Apoptosis in Lymphoblastic Leukemia Cell Line (C121)

Leukemia is known as the world's fifth most prevalent cancer. New cytotoxic drugs have created considerable progress in the treatment, but side effects are still the important cause of mortality. Plant derivatives have been recently considered as important sources for the treatment of various diseases, including cancer. Gallic acid (GA) is a polyhydroxyphenolic compound with a wide range of biological functions. The aim of the present study was to evaluate the effect of GA on proliferation inhibition and apoptosis induction of a lymphoblastic leukemia cell line. Jurkat cell (C121) line was cultured in RPMI 1640 supplemented with 10% heat-inactivated fetal bovine serum (FBS) with different concentrations of GA (10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 mu M) for 24, 48 and 72 hours. The effect of GA on cell viability was measured using MTS assay. Induction of apoptosis was evaluated with Annexin V-FITC/PI kit and flow cytometry. Data were analyzed by SPSS version 20 using Kruskal-Wallis and Dunn's multiple comparison tests. Decline of cell viability to less than 50% was observed at 60.3+/-1.6, 50.9+/-1.5, and 30.9+/-2.8 mu M concentration after 24, 48, and 72 hours incubation, respectively. All concentrations of GA (10, 30, 50 and 80 mu M) enhanced apoptosis compared to the control (P<0.05). The results demonstrate that the polyphenolic compound, GA, is effective in inhibition of proliferation and induction of apoptosis in Jurkat cell line. It is recommended to study the mechanism of apoptosis induction in future investigations

The Inhibitory Effect of Epigallocatechin Gallate on the Viability of T Lymphoblastic Leukemia Cells is Associated with Increase of Caspase-3 Level and Fas Expression

Acute lymphoblastic leukemia is the most prevalent cancer in children. Novel components to help struggle aggressive malignancies and overcome some side effects of conventional treatments could be a promising strategy. Epigallocatechingallate (EGCG), have attracted the attention of scientists for prevention or treatment of some cancers. Jurkat cells were incubated with the different concentrations of EGCG (30–100 µm) for 24, 48, and 72 h and cell viability was investigated using MTS test. Apoptosis and the level of caspase 3 alterations were evaluated using flowcytometry and expression of Fas by Real Time PCR. EGCG decreased viability of cells with an inhibition concentration (IC50) of 82.8 ± 3.1, 68.8 ± 4 and 59.7 ± 4.8 μM in 24,48 and 72 h. 50, 70 and 100 µM concentrations of EGCG induced apoptosis in about 31, 40 and 71% of the cells, respectively. The mean value of caspase 3 positive cells in the presence of 50, 70 and 100 µm concentrations of EGCG was 19.3 ± 2.9, 29.5 ± 3.1 and 61.2 ± 3.4 respectively compared to 7.8 ± 1.1 in control with a significant difference at 100 µm concentration. Treatment with EGCG for 48 h enhanced the expression of Fas reaching to a significant level at 100 µM concentration. EGCG is effective in decrease cell viability, apoptosis induction and enhancement of caspase 3 and Fas expression level in jurkat cells. A comprehensive understanding of molecular events and pharmacokinetics of the component and experiments in animal models are required for dose determination and its interaction with other components of combination chemotherapy

Frequency of T lymphocyte subsets in major beta-thalassemia patients and the influencing factors

زمینه و هدف: از راهکارهای رایج درمانی در بیماران تالاسمی تزریق خون های مکرر و درمان دفع آهن است. عوارض عفونی از مشکلات جدی در بیماران تالاسمی به حساب می آید که می تواند ناشی از ناهنجاری های ایمیونولوژیکی باشد. در مطالعه حاضر فراوانی زیر گروه های اصلی لنفوسیت های T و ارتباط آن ها با سن، میزان تزریق خون، فریتین سرم و درمان دفع آهن مورد بررسی قرار گرفته است. روش بررسی: در این مطالعه توصیفی- مقطعی 27 بیمار مبتلا به تالاسمی ماژور مراجعه کننده به بیمارستان هاجر شهرکرد در سال 1390 با محدوده سنی 30-10 سال که بر اساس معیارهای بالینی و آزمایشگاهی تشخیص داده شده بودند، شرکت کردند. گروه شاهد نیز شامل یک گروه 26 نفره از افراد سالم بودند که از لحاظ سن و جنس با بیماران مطابقت داشتند. نمونه خون وریدی در لوله های حاوی سدیم هپارین جمع آوری و پس از لیز گلبول های قرمز با آنتی بادی های منوکلونال نشاندار فلورسنت رنگ آمیزی گردید و مورد آنالیز فلوسایتومتریک قرار گرفت. تعداد سلول ها با توجه به نتایج آنالیز فوق و شمارش خونی محاسبه گردید. نتایج در نرم افزار SPSS و با استفاده از آزمون های M‏ann-Withney و همبستگی اسپیرمن تجزیه و تحلیل شدند. یافته ها: تعداد مطلق لنفوسیت ها در بیماران به صورت معنی داری بیش از گروه شاهد و درصد لنفوسیت های T به صورت معنی داری کمتر از گروه شاهد بود (001/0>P) . تعداد لنفوسیت های T در هر دو گروهCD4 و CD8 بین بیماران و گروه شاهد تفاوت معنی داری نداشت (05/

Effect of Epigallocatechin-3-gallate (EGCG) on cell proliferation inhibition and apoptosis induction in lymphoblastic leukemia cell line

Introduction: Acute lymphoblastic leukemia (ALL) is one of the malignant proliferations of lymphoid cells in the early stages of differentiation and accounts for &frac34; of all cases of childhood leukemia. Available treatment cannot completely treat this disease. Epigallocatechin-3-gallate (EGCG) is a polyphenolic compounds in the green tea that has demonstrated to have anticancer and antimitotic properties. The purpose of the present study was the evaluation of the effect of EGCG on the proliferation inhibition and apoptosis induction in a lymphoblastic leukemia cell line. Methods: Jurkat cell line was cultured in standard condition and in different concentrations of EGCG (0-100 micromolar) for 24, 48 and 72 hours. Cell viability was measured by MTS assay. Apoptosis induction was assessed by annexin V-FITC and flow cytometry analysis. Results: The MTS assay revealed that EGCG has decreased cell viability with a time and dose dependent manner. The level of cell apoptosis in all used concentrations of EGCG (50, 70 and 100 &mu;m) was higher than control group (71, 40 and 31 respectively vs. 8) and reached to significant level at 100 &mu;m concentration. Conclusion: The study indicated that EGCG is effective on proliferation inhibition and apoptotic induction in Jurkat lymphoblastic cell line. Therefore, the study of the mechanism of apoptosis induction could be a step of progress toward target therapy which might be considered in the future studies.</p

The effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells

ntroduction: Prostate cancer is the second leading cause of cancer-related deaths and the mostcommon cancer diagnosed in men in the United States and Europe. Hesperetin, a member of thef lavonoids with antioxidant property, is found in fruits such as oranges and red fruits. This study was undertaken to evaluate the effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells.Methods: PC3 cell line was cultured in standard condition. The cells were exposed to differentconcentrations of hesperetin (0-1000 μM) for 48 hours. Cell viability was measured by MTT assay.Apoptosis induction was assessed by Annexin V-FITC by flow cytometry analysis.Results: The PC3 cells exposed to hesperetin (0-1000 μM) exhibited an IC (inhibitoryconcentration of 50%) about 450 μM. At different concentrations of hesperetin (400, 450 and 500µm), the apoptosis increased slightly (not significant) in treated PC3 cells compared to the controlgroup (5.4%, 7.8% and 9.1% respectively vs. 4.2%).Conclusion: These results clearly show that hesperetin can lead to inhibition of PC3 cellsproliferation

Evaluation of the Simultaneous Effects of Lactobacillus delbrueckii and L. lactis on Biofilms of Isolates from Chronic Ulcer Infections with Multiple-drug Resistance

Background: Bacterial biofilm is a major barrier to chronic wound healing. Therefore, the prevention of biofilm formation has an effective role in accelerating the healing of these wounds. Today, probiotics’ anti-biofilm and antibacterial activity have been proven, and bacteriotherapy by probiotics is a new strategy for treating chronic ulcer infections. Objectives: The present study aimed to investigate the synergistic effects of Lactobacillus delbrueckii and L. lactis on biofilms of bacterial agents isolated from these ulcers in the human plasma biofilm model (hpBIOM). Methods: This study examined 82 specimens of chronic ulcer biofilms and identified bacterial isolates using phenotypic and molecular methods. After preparing the hpBIOM, 50 µL of each probiotic (109 CFU/mL) was added in two doses separately and simultane-ously. After 24 hours, 1 mL of bromelain (0.1 g/mL) was added to the complex and incubated at 37°C for two hours. Then, the surviving bacterial cells were counted by serial dilutions. Results: Among 119 bacterial isolates, Staphylococcus aureus (19%), Escherichia coli (17.0%), and Pseudomonas aeruginosa (14%) were the most common bacterial isolates. Lactobacillus delbrueckii showed anti-biofilm activity against multiple-drug resistance pathogens, Staphylococcus, P. aeruginosa, and K. pneumoniae. Although L. lactis had anti-biofilm activity against these three pathogens, its effect was less than that of L. delbrueckii. The two probiotics did not have any synergistic effect on the biofilms of the isolates. Conclusions: The results of the present study emphasized the potential of probiotics in destroying biofilms of isolates with multiple-drug resistance; however, their simultaneous use for this purpose requires further investigation

Biological effects of hesperetin on Interleukin-6/phosphorylated signal transducer and activator of transcription 3 pathway signaling in prostate cancer PC3 cells

Interleukin-6 (IL-6) is a multifunctional glycoprotein that regulates the growth of some tumors, including prostate carcinomas due to signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinases 1/2 (ERK1/2), and AKT signaling pathways. Hesperetin, as a flavanone, has several biological properties such as antitumor and anti-inflammatory. Objective: This study was carried out to evaluate the biological effects of hesperetin on the IL-6 gene expression and phosphorylated STAT3, AKT, and ERK1/2 signaling pathways in PC3 prostate cancer (PC) cells. Materials and Methods: In this study, we used real-Time quantitative polymerase chain reaction (RT-qPCR) and ELISA to evaluate IL-6 gene expression and IL-6 protein secretion, respectively, in the treated PC3 cells with 0, 400, 450, and 500 μM of hesperetin. Cell survival studies were done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after 48 h treatment with hesperetin, and cell apoptosis was determined by flow cytometry. The protein levels of activated signaling molecules (pSTAT3, pAKT, and pERK1/2) analyzed by immunoprecipitation technique. Results: Hesperetin-Treated PC3 cells resulted in reduction of cell viability. Hesperetin led to the elevation of phosphorylated STAT3, ERK1/2, and AKT signaling proteins after 48 h in a dose-dependent manner as compared to the control cells. IL-6 gene expression, as well as protein level, significantly increased (P < 0.05) in a dose-dependent pattern in treated PC3 with hesperetin compared to the control cells. Further, hesperetin exposure resulted in the induction of cell cycle arrest at G0/G1 phase. Conclusion: Hesperetin in PC3 cells led to elevation IL-6 gene expression, IL-6 protein secretion, pSTAT3, pERK1/2 and pAKT intracellular signaling proteins. Our results indicate that hesperetin treatment leads to the inhibition of cell proliferation and the induction of cell cycle arrest at the G1 phase. Hesperetin can be considered a potent agent which synchronizes and stops cell cycle at G0/G1 phase to apply suitable chemotherapeutic agents and radiotherapy in PC cells

PD-1/PD-L1 Interaction Regulates BCL2, KI67, BAX, and CASP3, Altering Proliferation, Survival, and Apoptosis in Acute Myeloid Leukemia

Programmed death ligand-1 (PD-L1) is a pivotal inhibitory checkpoint ligand known to induce T-cell exhaustion via interaction with the programmed death‑1 (PD‑1) receptor. Beyond this, PDL1’s intrinsic signaling pathways within cancer cells warrant further exploration. This study aims to elucidate the effect of PD-L1 stimulation on the proliferation, survival, and apoptosis of acute myeloid leukemia (AML) cell lines. Two human AML cell lines, HL-60 and THP-1 were cultured and treated with phorbol 12-myristate 13-acetate (PMA) to induce PD-L1overexpression. Post-treatment PD-L1 expression was confirmed via flow cytometry. Subsequently, cell surface PD-L1 was stimulated using a recombinant PD-1, 24 hours post-PMA treatment. The expression alterations in pivotal genes including BCL2, MKI67, BAX, and CASP3 were monitored using quantitative real-time polymerase chain reaction 24 and 48 hours post-treatment. Additionally, annexin-V through flow cytometry. Findings reveal that PD-L1 stimulation augments AML cell proliferation and survival by enhancing MKI67 and BCL2 expressions while concurrently inhibiting cell apoptosis due to decreased BAX and CASP3 expression following PD-L1 stimulation. Notably, stimulated cells expressed exhibited reduced annexin-V compared to control cells. This study underscores that PD-L1 stimulation fosters AML cell proliferation and survival while impeding cell apoptosis. The results hold potential implications for targeting PD-L1 in AML treatment strategies