曲古抑菌素A对肺癌细胞株H322抑制效应及机制的研究

目的 评价曲古抑菌素A(TSA)对肺癌细胞株H322的生长抑制效应及机制.方法 以四氮甲基唑蓝、流式细胞术观察TSA作用后,肺癌细胞株H322的生长抑制情况以及细胞周期、细胞凋亡等变化,Western blot分析细胞周期相关蛋白p21、抗凋亡蛋白survivin及细胞外信号调节激酶(ERK)的表达.结果 TSA对H322具有时间依赖性和浓度依赖性的生长抑制作用;TSA作用48h及96h后,H322细胞凋亡及G2/M期细胞明显增加(P＜0.05).p21蛋白表达水平显著提高,survivin蛋白及磷酸化ERK蛋白表达显著下降.结论 TSA对肺癌细胞株H322生长具有抑制作用,其机制可能是上调p21蛋白的表达,引起细胞周期的阻滞;同时抑制survivin的表达,阻断ERK信号通路,导致细胞凋亡.     

曲古抑菌素A对鼻咽癌CNE3细胞增殖抑制作用

目的 探讨曲古抑菌素A(TSA)对鼻咽癌CNE3细胞周期阻滞与凋亡影响及作用机制.方法 以不同浓度TSA作用鼻咽癌CNE3细胞株,采用甲基噻唑基四唑(MTT)法检测细胞生长抑制率;流式细胞术测定TSA作用前后鼻咽癌细胞调亡情况及细胞周期变化;逆转录-聚合酶链反应(RT-PCR)分析鼻咽癌细胞中细胞周期素依赖性蛋白激酶相互作用蛋白1(p21)mRNA表达的变化.结果 100～500 nmol/L TSA对CNE3细胞生长有明显抑制作用,呈剂量依赖性,抑制率为17.74%～44.33%;400,500 nmol/L TSA可在DNA合成期(S)、DNA合成后期/有丝分裂期(G2/M)诱导CNE3细胞周期阻滞,并诱导细胞凋亡,24 h凋亡率为(14.67±0.21)%,(18.73±1.80)%,48 h凋亡率分别为(16.3±0.96)%,(39.17±1.27)%,与对照组(9.16±1.05)%比较差异均有统计学意义(P<0.05);TSA可诱导CNE3细胞内p21基因表达.结论 TSA可明显抑制CNE3细胞增殖,诱导细胞凋亡,其作用机制与p21基因异常表达有关.     

p53蛋白在苯并(a)芘诱导的p21、E2F-1表达及细胞周期改变中的作用

目的 探讨p53蛋白在苯并(a)芘[benzo(a)pyrene,B(a)P]诱导的人胚肺成纤维细胞(HELF)细胞周期改变中的作用及其与p21、E2F-1的关系.方法 转染p53 siRNA质粒(p53-H)和载体CMV的HELF细胞(HELF/CMV)无血清培养48 h后,加入2 μmol/L B(a)P作用24 h.用流式细胞仪检测细胞周期的变化.用Western blotting检测细胞中p53、p21蛋白含量的改变,利用细胞核、细胞浆分离技术观察其亚细胞定位.用免疫荧光法观察E2F-1蛋白含量及细胞核、细胞浆分布.利用p53 siRNA质粒和化学抑制剂pifithrin-α(PFT)抑制其表达,观察p53与p21、E2F-1的上下游关系以及其在B(a)P引起的细胞周期改变中的作用.结果 2 μmol/L B(a)P作用24 h后,G1期细胞比例由(71±5)%减少为(39±4)%;p53、p21以及E2F-1蛋白含量增加,并且主要分布在细胞核内.用p53 siRNA质粒和PFT抑制p53表达后,B(a)P诱导的p21高表达被抑制,细胞核内的含量明显减少;B(a)P诱导的E2F-1蛋白含量增加以及细胞周期的改变没有明显变化.结论 B(a)P通过p53非依赖的信号通路引起HELF细胞周期的改变;p53对p21的表达具有调节作用,而对E2F-1的表达不具有调节作用.     

绿色咖啡豆可制取抗HIV-1新药

美国加利福尼亚大学的研究者报道,从绿色咖啡豆提取的菊苣酸能通过抑制Ⅰ型人免疫缺陷病毒(HIV-1)整合酶而抑制HIV-1在CD4 T细胞中的复制。HIV-1整合酶、蛋白酶和逆转录酶是HIV-1感染正常细胞时所     

苯丁酸钠对宫颈癌Hela细胞增殖及p21WAF1/CIP1和CDK7表达的影响

目的:探讨苯丁酸钠(SPB)在体外诱导宫颈癌Hela细胞生长抑制和细胞周期阻滞以及对p21WAF1/CIP1和CDK7基因表达的影响。方法:体外培养Hela细胞,应用MTT法检测苯丁酸钠对Hela细胞增殖的影响,流式细胞仪分析细胞周期的变化,半定量RT-PCR法检测细胞p21WAF1/CIP1和CDK7基因表达水平。结果:苯丁酸钠明显抑制Hela细胞增殖,呈时间-剂量依赖性;苯丁酸钠诱导Hela细胞周期阻滞于G0/G1期,使S期细胞数减少;苯丁酸钠促进抑癌基因p21WAF1/CIP1的表达,对CDK7基因的表达有抑制作用。结论:苯丁酸钠在体外抑制宫颈癌Hela细胞的增殖,使之阻滞于G0/G1期,可能与上调p21WAF1/CIP1基因表达、下调CDK7基因表达有关。     

吗啡对HIV-1在MT2细胞内复制影响

目的 探讨吗啡对人类免疫缺陷病毒-1(HIV-1)在MT2细胞中复制的影响.方法 将MT2细胞按单纯随机分组的原则分为吗啡处理组、吗啡+纳洛酮处理组、纳洛酮处理组和病毒对照组,先用浓度为10-8 mol/L的纳洛酮预处理吗啡+纳洛酮处理组和纳洛酮处理组0.5h,再用10-12、10- 10和10-8 mol/L 3个浓度的吗啡处理吗啡+纳洛酮处理组和吗啡处理组24h,然后每组细胞加入HIV -1感染MT2细胞,并分别于感染的第3、4、5和6d取培养上清测定HIV -1 p24抗原表达.结果 HW-1感染MT2细胞第3、4、5、6d,10-12、10-10和10-8 mol/L 3个浓度吗啡处理组的HIV-1 p24抗原表达均高于病毒对照组,差异均有统计学意义(P＜0.01);吗啡+纳洛酮处理组、纳洛酮处理组与病毒对照组HIV-1 p24抗原表达比较,差异均无统计学意义(P＞0.05);第3、4、5、6d,3个浓度吗啡处理组的HIV-1 p24抗原表达量比对照组增加的倍数比较,差异均有统计学意义(P＜0.05);10-12、10-10和10-8 mol/L 3个浓度吗啡处理组在不同时间HIV-1 p24抗原表达量比对照组增加倍数比较,3个吗啡处理组的HIV-1 p24抗原表达量比对照组增加倍数均随着感染时间的延长而呈现递增的趋势(P＜0.05).结论 吗啡能够促进HIV-1在MT2细胞和内的复制,并且随感染时间的延长呈现递增趋势;吗啡促进HIV-1复制的作用可被阿片受体阻滞剂纳洛酮阻断.     

沉默lncRNA MAFG-AS1对人卵巢癌细胞增殖和凋亡的影响及分子机制

目的探讨沉默lncRNA MAFG-AS1对人卵巢癌细胞增殖和凋亡的影响及分子机制。方法 qRT-PCR检测正常卵巢上皮细胞HOSE和3种卵巢癌细胞(SKOV3、HO8910、OVCAR3)中MAFG-AS1和miR-143-3p的表达。荧光素酶报告基因检测和qRT-PCR验证MAFG-AS1与miR-143-3p的靶向调控关系。以SKOV3细胞为研究对象,分别构建沉默MAFG-AS1或过表达miR-143-3p的卵巢癌细胞株。应用MTT法检测细胞活力,应用流式细胞术检测细胞凋亡情况,应用Western Blot检测增殖相关蛋白Cyclin D1和p21及凋亡相关蛋白Bcl-2及Bax的表达。结果与HOSE组比较,3种卵巢癌细胞中MAFG-AS1的表达显著上调,miR-143-3p的表达显著下调。pc DNA组、pc DNA-MAFG-AS1组、si-NC组、si-MAFG-AS1组miR-143-3p表达水平比较差异有统计学意义(P0.05)。miR-143-3p是MAFG-AS1的靶基因,MAFG-AS1可负性调控miR-143-3p的表达。沉默MAFG-AS1或过表达miR-143-3p均可抑制卵巢癌细胞的增殖,促进细胞凋亡,抑制Cyclin D1和Bcl-2蛋白表达,促进p21和Bax蛋白表达。抑制miR-143-3p表达可逆转沉默MAFG-AS1对卵巢癌细胞的增殖抑制和凋亡促进作用。结论沉默MAFGAS1通过上调miR-143-3p表达可抑制卵巢癌细胞的增殖,促进细胞凋亡。     

Nkx3.1和p27协同诱导激素抵抗性前列腺癌PC3细胞株凋亡的研究

目的 探讨人类同源框基因Nkx3.1和细胞周期素依赖激酶抑制剂p27诱导激素抵抗前列腺癌PC3细胞凋亡的协同作用.方法 构建Nkx3.1和p27的真核表达质粒载体,恢复表达PC3细胞Nkx3.1或/和p27表达.Nkx3.1或p27单独和二者结合转染PC3细胞后,检测细胞增殖、细胞周期和细胞凋亡,同时分析了凋亡相关蛋白...     

原发性胆囊癌组织中细胞凋亡及相关基因蛋白产物的表达

目的探讨原发性胆囊癌组织中细胞凋亡及相关基因蛋白Bcl-2及p21WAF1的表达.方法用免疫组化ABC法检测46例原发性胆囊癌不同组织学分级中p21WAF1和 Bcl-2的表达,TUNAL法检测细胞凋亡的发生.结果在原发性胆囊癌中随着组织学分级的增加,细胞凋亡率减少,并且p21WAF1表达减弱,而Bcl-2表达增强,差异均有统计学意义(P<0.05);相关分析显示细胞凋亡率与p21WAF1表达呈正相关(r=0.52,P<0.05),与Bcl-2表达呈负相关(r=-0.58,P<0.05).结论细胞凋亡对原发性胆囊癌的发生发展有着重要影响,p21WAF1及Bcl-2基因参与胆囊癌的发生和发展.     

细胞周期调控基因p21~(WAF1/CIP1)与宫颈癌

p21WAF1/CIP1基因是1993年发现并克隆的细胞周期依赖性蛋白激酶抑制因子(Cyclin-dependent kinas inhibitor,CDKI)的家族成员,与p21ras不同,它参与细胞的多种功能活动。近年的许多研究表明,p21WAF1/CIP1基因与宫颈癌的发生、发展关系密切,从而引起学者的关注。1p21WAF1/CIP1基因的发现与命名p21WAF1/CIP1基因是在不同实验室用不同的方法克隆出来的。Harper等〔1〕从细胞周期出发寻找CDK调节蛋白时,发现一种可与细胞周期依赖性蛋白激酶(cyclin-depedent kinase,CDK)相互作用的蛋白,并将其克隆,命名为CDK相互作用蛋白(cyclin-…     

中国HIV感染者VPR序列变异对细胞周期和致凋亡作用的影响 FREE

目的研究带有不同变异位点的人免疫缺陷病毒1型（HIV 1）vpr基因对感染细胞周期和凋亡的影响,以及其致细胞周期变化和致细胞凋亡的机制间的可能关系。方法以14个带有HIV 1 vpr基因片段的pcDNA3.1（+）真核表达载体构建重组质粒,将其转染Hela细胞,并设立保守株vpr基因转染细胞、突变株vpr FS基因转染细胞、空载体转染细胞和未转染细胞作为对照,经逆转录多聚酶链式反应（RT PCR）检测目的基因转染成功后,Pi染色,用流式细胞仪检测被转染细胞的细胞周期分布和细胞凋亡率。结果14个带有不同变异位点HIV 1 vpr基因片段的Hela细胞经流式细胞仪检测,显示出不同的致细胞周期阻滞和致细胞凋亡的能力。发现转染保守片段HIV 1 vpr的Hela细胞,其细胞周期出现G2期阻滞和细胞凋亡率明显升高,但转染vpr C末端截断的vpr FS片段的细胞、空载体pcDNA3.1（+）转染细胞和未转染的Hela细胞无此现象。转染了HIV 1 vpr基因序列相对应的Vpr蛋白中含有70V、85P、86G、94G突变的片段,较vpr保守片段致感染细胞G2期阻滞和凋亡的能力明显下降。初步发现vpr诱导G2期阻滞百分率越高,其所致凋亡率亦越高。结论HIV 1vpr基因有明显的致感染细胞G2周期阻滞和致细胞凋亡的作用,但vpr C末端截断的vpr FS片段无此功能。说明中国感染者HIV 1 vpr基因表达蛋白的70V、85P、86G、94G位点突变能使其致感染细胞G2期阻滞和凋亡的能力下降。vpr诱导G2期阻滞的程度与其致凋亡水平可能相关,提示两者的发生机制可能有一定的关联。本研究为进一步探讨HIV 1致病机制和探索可能的基因干预措施打下了基础。     

Epicatechin Gallate Induces Cell Death via p53 Activation and Stimulation of p38 and JNK in Human Colon Cancer SW480 Cells

The tea flavonoid epicatechin gallate (ECG) exhibits a wide range of biological activities. In this study, the in vitro anticancer effects of ECG on SW480 colon cancer cell line was investigated by analyzing the cell cycle, apoptosis, key proteins involved in cellular survival/proliferation, namely AKT/phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinases (MAPKs), and the role of p53 in these processes. ECG induced cell cycle arrest at the G0/G1-S phase border associated with the stimulation of p21, p-p53, and p53 and the suppression of cyclins D1 and B1. Exposure of SW480 cells to ECG also led to apoptosis as determined by time-dependent changes in caspase-3 activity, MAPKs [extracellular regulated kinase (ERK), p38, and c-jun amino-terminal kinase (JNK)], p21 and p53 activation, and AKT inhibition. The presence of pifithrin, an inhibitor of p53 function, blocked ECG-induced apoptosis as was manifested by restored cell viability and caspase-3 activity to control values and reestablished the balance among Bcl-2 anti- and proapoptotic protein levels. Interestingly, ECG also inhibited p53 protein and RNA degradation, contributing to the stabilization of p53. In addition, JNK and p38 have been identified as necessary for ECG-induced apoptosis, upon activation by p53. The results suggest that the activation of the p53-p38/JNK cascade is required for ECG-induced cell death in SW480 cells.     

Pretreatment with rituximab enhances radiosensitivity of non-Hodgkin's lymphoma cells

The present study examines the effects of ionizing radiation in combination with rituximab (RTX), a chimeric human anti-CD20 monoclonal antibody, on proliferation, cell cycle distribution and apoptosis in B-lymphoma RL and Raji cells. Exposure to ionizing radiation (9 Gy) induced cell growth delay and apoptosis in RL cells, whereas Raji cells showed moderate radio-resistance. The simultaneous exposure of lymphoma cells to ionizing radiation and RTX (10 microg/mL) markedly enhanced apoptosis and cell growth delay in RL and Raji cells. Cooperative antiproliferative and apoptotic effects of RTX and radiation were achieved through the inhibition of c-myc and bcl-XL expression. Furthermore, RTX-modulated expression of cell cycle regulating proteins, such as p53, p21/WAF1, p27/KIP1, contributed to the development of radiation-induced cell killing and growth arrest. Each NHL cell line that underwent apoptosis induced by combination treatment revealed enhanced caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage as compared to only irradiated cells. These findings show that rituximab synergistically enhances radiation-induced apoptosis and cell growth delay through the expression of proteins involved in the programmed cell death and cell cycle regulation pathways.     

外源性p21（waf1）基因转染对人胃癌细胞系BGC-823增殖的影响

目的：探讨外源性p21waf1基因转染对人胃癌细胞系BGC-823细胞增殖的影响。方法：用脂质体介导的方法将pIRES-p21waf1真核表达载体转染人胃癌细胞系BGC-823,分为pIRES-p21waf1转染组、pIRES-neo空载体组及未转染组三个组别。应用实时荧光定量RT-PCR、Westernblot免疫印迹分别在基因和蛋白两个水平检测各组p21的表达情况,采用四甲基偶氮唑蓝（MTT）法测定细胞增殖能力,流式细胞仪分析细胞DNA周期变化,所有数据进行统计学分析。结果：p21waf1转染组p21waf1mRNA和p21蛋白高表达（P〈0.01）;p21waf1转染组BGC-823细胞生长速度明显低于空载体组和未转染组（P〈0.01）;流式细胞仪观察到p21waf1转染组细胞的G1期细胞比例显著高于空载体组和未转染组（P〈0.01）,S期比例显著低于空载体组和未转染组（P〈0.01）,并出现凋亡峰。结论：p21waf1基因转染可以抑制人胃癌细胞系BGC-823细胞增殖并能诱导其发生细胞凋亡,可能为胃癌的基因治疗提供一条新的途径。     

Genistein‐induced G2‐m arrest,P21WAF1 upregulation,and apoptosis in a non‐small‐cell lung cancer cell line

Lung cancer is the leading cause of cancer‐related death in the world, with increasing incidence in many developed countries. Epidemiological data suggest that consumption of soy products (the isoflavone genistein) may be associated with a decreased risk of breast and prostate cancer; however, such studies are not available for lung cancer. We investigated cell growth inhibition, modulation in gene expression, and induction of apoptosis by genistein in H460 non‐small lung cancer cells. Genistein inhibited H460 cell growth in a dose‐dependent manner. Flow‐cytometric analysis showed that 30 μM genistein arrested cell cycle progression at the G2‐M phase. 4,6‐Diamidino‐2‐phenylindole staining, flow‐cytometric analysis, and DNA laddering were used to investigate apoptotic cell death, and the results show that 30 μM genistein can cause typical DNA laddering, a hallmark for apoptosis. In addition, flow cytometry and 4,6‐diamidino‐2‐phenylindole staining showed induction of apoptosis by genistein. Our investigation also demonstrated the modulation of p21^WAF1 by Western blot analysis of cell lysates obtained from cultured cells treated with 30 and 50 μM genistein for 24, 48, and 72 hours. Simultaneously, im‐munocytochemical staining was conducted for the expression of p21^WAF1 protein. Our results showed that genistein can upregulate p21^WAFI expression in genistein‐treated cells. From these results, we conclude that genistein may act as an anticancer agent, and further studies may prove its efficacy in non‐small lung cancer cells. Thus the biological effects of genistein may, indeed, be due to the modulation of cell growth, cell death, and cell cycle regulatory molecules.     

Grifola frondosa Glycoprotein GFG-3a Arrests S phase,Alters Proteome,and Induces Apoptosis in Human Gastric Cancer Cells

GFG-3a is a novel glycoprotein previously purified from the fermented mycelia of Grifola frondosa with novel sugar compositions and protein sequencing. The present study aims to investigate its effects on the cell cycle, differential proteins expression, and apoptosis of human gastric cancer SGC-7901 cells. Our findings revealed that GFG-3a induced the cell apoptosis and arrested cell cycle at S phase. GFG-3a treatment resulted in the differential expression of 21 proteins in SGC-7901 cells by upregulating 10 proteins including RBBP4 associated with cell cycle arrest and downregulating 11 proteins including RUVBL1, NPM, HSP90AB1, and GRP78 involved in apoptosis and stress response. qRT-PCR and Western blot analysis also suggested that GFG-3a could increase the expressions of Caspase-8/-3, p53, Bax, and Bad while decrease the expressions of Bcl2, Bcl-xl, PI3K, and Akt1. These results indicated that the stress response, p53-dependent mitochondrial-mediated, Caspase-8/-3-dependent, and PI3k/Akt pathways were involved in the GFG-3a-induced apoptosis process in SGC-7901 cells. These findings might provide a basis to prevent or treat human gastric cancer with GFG-3a and understand the tumor-inhibitory molecular mechanisms of mushroom glycoproteins.     

Mechanisms of benzene-induced hematotoxicity and leukemogenicity: cDNA microarray analyses using mouse bone marrow tissue

Although the mechanisms underlying benzene-induced toxicity and leukemogenicity are not yet fully understood, they are likely to be complicated by various pathways, including those of metabolism, growth factor regulation, oxidative stress, DNA damage, cell cycle regulation, and programmed cell death. With this as a background, we performed cDNA microarray analyses on mouse bone marrow tissue during and after a 2-week benzene exposure by inhalation. Our goal was to clarify the mechanisms underlying the hematotoxicity and leukemogenicity induced by benzene at the level of altered multigene expression. Because a few researchers have postulated that the cell cycle regulation mediated by p53 is a critical event for benzene-induced hematotoxicity, the present study was carried out using p53-knockout (KO) mice and C57BL/6 mice. On the basis of the results of large-scale gene expression studies, we conclude the following: (a) Benzene induces DNA damage in cells at any phase of the cell cycle through myeloperoxidase and in the redox cycle, resulting in p53 expression through Raf-1 and cyclin D-interacting myb-like protein 1. (b) For G1/S cell cycle arrest, the p53-mediated pathway through p21 is involved, as well as the pRb gene-mediated pathway. (c) Alteration of cyclin G1 and Wee-1 kinase genes may be related to the G2/M arrest induced by benzene exposure. (d) DNA repair genes such as Rad50 and Rad51 are markedly downregulated in p53-KO mice. (e) p53-mediated caspase 11 activation, aside from p53-mediated Bax gene induction, may be an important pathway for cellular apoptosis after benzene exposure. Our results strongly suggest that the dysfunction of the p53 gene, possibly caused by strong and repeated genetic and epigenetic effects of benzene on candidate leukemia cells, may induce fatal problems such as those of cell cycle checkpoint, apoptosis, and the DNA repair system, finally resulting in hemopoietic malignancies. Our cDNA microarray data provide valuable information for future investigations of the mechanisms underlying the toxicity and leukemogenicity of benzene.     

Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.     

In silico analysis of molecular interactions between HIV-1 glycoprotein gp120 and TNF receptors

Proinflammatory microenvironmental is crucial for the Human Immunodeficiency Virus Type 1 (HIV-1) pathogenesis. The viral glycoprotein 120 (gp120) must interact with the CD4+ T cell chemokine receptor (CCR5) and a co-receptor C-X-C chemokine receptor type 4 (CXCR4) to let the virus entry into the host cells. However, the interaction of the viral particle with other cell surface receptors is mandatory for its attachment and subsequently entry. Tumor Necrosis Factor receptor type I (TNFR1), type II (TNFR2) and Fas are a superfamily of transmembrane proteins involved in canonical inflammatory pathway and cell death by apoptosis as responses against viral pathogens. In our study, we performed an in silico evaluation of the molecular interactions between viral protein gp120 and TNF receptors (TNFR1, TNFR2 and Fas). Protein structures were retrieved from Protein Databank (PDB), and Molecular Docking and dynamics were performed using ClusPro 2.0 server and GROMACS software, respectively. We observed that gp120 is able to bind TNFR1, TNFR2 and Fas receptors, although only the TNFR2-gp120 complex demonstrated to produce a stable and durable binding. Our findings suggest that gp120 may act as an agonist to TNF-α and also function as an attachment factor in HIV-1 entry process. These molecular interaction by gp120 may be the key to HIV-1 immunopathogenesis. In conclusion, gp120 may stimulate pro-inflammatory and apoptotic signaling transduction pathways mediated by TNFR2 and may act as an attachment factor retaining HIV-1 viral particles on the host cell surface.     

Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells

Increased soy consumption in Asian diets, resulting in increased serum isoflavone levels, has been associated with a decreased risk for prostate adenocarcinoma (PCa). The isoflavone genistein is believed to be the anticancer agent found in soy, and significant levels of genistein have been detected in human prostatic fluid, implicating the role of genistein in PCa prevention. Recent studies have demonstrated genistein's ability to inhibit cell growth and induce apoptosis in several cell lines; however, the molecular mechanisms of genistein's effect are not known. We have evaluated the mechanism by which genistein may inhibit PCa cell growth. Here we report that genistein inhibits PCa cell growth in culture in a dose-dependent manner, which is accompanied by a G2/M cell cycle arrest. Cell growth inhibition was observed with concomitant downregulation of cyclin B, upregulation of the p21WAF1 growth-inhibitory protein, and induction of apoptosis. Collectively, these results provide experimental evidence for a novel effect of genistein on cell cycle gene regulation, resulting in the inhibition of cell growth and ultimate demise of tumor cells.