{"title":"睡茄提取物通过抑制幽门螺旋杆菌和爱泼斯坦-巴氏病毒产生的细胞环境中的甘氨肽,降低胃癌的致癌特性。","authors":"Dharmendra Kashyap, Rajarshi Roy, Nidhi Varshney, Budhadev Baral, Pranit Hemant Bagde, Meenakshi Kandpal, Sachin Kumar, Parimal Kar, Hem Chandra Jha","doi":"10.1080/07391102.2023.2252096","DOIUrl":null,"url":null,"abstract":"<p><p><i>Helicobacter pylori</i> and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that <i>H. pylori</i> and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of <i>Withania somnifera</i> root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on <i>H. pylori</i> and EBV-associated gene transcripts except for the lmps (<i>lmp1</i>, <i>lmp2a,</i> and <i>lmp2B</i>). Moreover, the WSE exert their anticancer activity <i>via</i> host cellular response and decreased the expression of cell-migratory (<i>mmp3</i> and <i>mmp7</i>); cell-cycle regulator (<i>pcna</i>); antiapoptotic gene (<i>bcl2</i>); increased the expression of the proapoptotic gene (<i>apaf1</i> and <i>bax</i>); and tumor suppressor (<i>p53</i>, <i>prb,</i> and <i>pten</i>). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with <i>H. pylori</i> and EBV.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>Withania somnifera</i> extract reduces gastric cancerous properties through inhibition of gankyrin in cellular milieu produced by <i>Helicobacter pylori</i> and Epstein Barr virus.\",\"authors\":\"Dharmendra Kashyap, Rajarshi Roy, Nidhi Varshney, Budhadev Baral, Pranit Hemant Bagde, Meenakshi Kandpal, Sachin Kumar, Parimal Kar, Hem Chandra Jha\",\"doi\":\"10.1080/07391102.2023.2252096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Helicobacter pylori</i> and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that <i>H. pylori</i> and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of <i>Withania somnifera</i> root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on <i>H. pylori</i> and EBV-associated gene transcripts except for the lmps (<i>lmp1</i>, <i>lmp2a,</i> and <i>lmp2B</i>). Moreover, the WSE exert their anticancer activity <i>via</i> host cellular response and decreased the expression of cell-migratory (<i>mmp3</i> and <i>mmp7</i>); cell-cycle regulator (<i>pcna</i>); antiapoptotic gene (<i>bcl2</i>); increased the expression of the proapoptotic gene (<i>apaf1</i> and <i>bax</i>); and tumor suppressor (<i>p53</i>, <i>prb,</i> and <i>pten</i>). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. 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引用次数: 0
摘要
幽门螺杆菌和eb病毒(EBV)是一类致癌物,它们在胃癌(GC)中的作用已得到证实。先前我们已经表明,幽门螺杆菌和EBV似乎通过上调癌蛋白甘肽来支持侵袭性胃癌的发生。天然植物活性分子具有阻断肿瘤发生的潜力。在此,我们研究了Withania somnifera根提取物(WSE)作为一种可能的化疗药物的潜力,以对抗宿主癌蛋白Gankyrin,该蛋白的表达被幽门螺杆菌和ebv相关的修饰细胞环境改变。结果表明,除了lmps (lmp1、lmp2a和lmp2B)外,WSE对幽门螺杆菌和ebv相关基因转录本没有任何抑制作用。此外,WSE通过宿主细胞反应发挥其抗癌活性,降低细胞迁移(mmp3和mmp7)的表达;细胞周期调节剂;抗凋亡基因bcl2;凋亡前基因(apaf1、bax)表达增加;肿瘤抑制因子(p53, prb, pten)。WSE治疗后,Gankyrin基因敲低也降低了TNF- α、Akt的表达,上调了NFkB、PARP、Casp3、Casp9的表达。WSE还减少了细胞迁移和基因组不稳定性,并迫使细胞进行程序性细胞死亡。此外,分子模拟研究表明,在WSE的8个活性化合物中,只有4个化合物,即withanolin A (WFA)、withanolide IV (WA4)、withanolide B (WNB)和withanolide D (WND)与Gankyrin有直接稳定的相互作用。本文首次报道了WSE治疗通过调节幽门螺杆菌和EBV共感染的胃上皮细胞的宿主细胞反应来降低癌变性质。由Ramaswamy H. Sarma传达。
Withania somnifera extract reduces gastric cancerous properties through inhibition of gankyrin in cellular milieu produced by Helicobacter pylori and Epstein Barr virus.
Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps (lmp1, lmp2a, and lmp2B). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory (mmp3 and mmp7); cell-cycle regulator (pcna); antiapoptotic gene (bcl2); increased the expression of the proapoptotic gene (apaf1 and bax); and tumor suppressor (p53, prb, and pten). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.