Kaposi's Sarcoma-Associated Herpesvirus-Positive Primary Effusion Lymphoma Tumor Formation in NOD/SCID Mice Is Inhibited by Neomycin and Neamine Blocking Angiogenin's Nuclear Translocation

Bottero, Virginie; Sadagopan, Sathish; Johnson, Karen E.; Dutta, Sandeep; Veettil, Mohanan Valiya; Chandran, Bala

doi:10.1128/jvi.01920-13

Cited by 24 publications

(18 citation statements)

References 88 publications

(141 reference statements)

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“…Induction of KSHV lytic cycle was achieved with either TPA (20 ng/ml) or neomycin (200 M) (17)(18)(19), as indicated. TREX-BCBL-1-RTA cells were induced with doxycycline (DOX) at a final concentration of 1 g/ml.…”

Section: Cellsmentioning

confidence: 99%

“…The nucleus of these cells have Ͼ80 copies of the episomal KSHV genome during latency, and the lytic replication cycle can be induced by treatment with chemical inducers such as 12-O-tetradecoylphorbol-13-acetate (TPA), sodium butyrate, or the aminoglycoside antibiotic neomycin (16)(17)(18)(19). Another well-established method to induce latent B cells is overexpression of the KSHV open reading frame 50 (ORF50) gene product RTA, which functions as a crucial latent-to-lytic switch protein (20).…”

mentioning

confidence: 99%

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Nuclear Innate Immune DNA Sensor IFI16 Is Degraded during Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus (KSHV): Role of IFI16 in Maintenance of KSHV Latency

Roy

Dutta

Iqbal

et al. 2016

J Virol

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IMPORTANCELike all herpesviruses, latency is an integral part of the life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV), an etiological agent for many human cancers. Herpesviruses utilize viral and host factors to successfully evade the host immune system to maintain latency. Reactivation is a complex event where the latent episomal viral genome springs back to active transcription of lytic cycle genes. Our studies reveal that KSHV has evolved to utilize the innate immune sensor IFI16 to keep lytic cycle transcription in dormancy. We demonstrate that IFI16 binds to the lytic gene promoter, acts as a transcriptional repressor, and thereby helps to maintain latency. We also discovered that during the late stage of lytic replication, KSHV selectively degrades IFI16, thus relieving transcriptional repression. This is the first report to demonstrate the role of IFI16 in latency maintenance of a herpesvirus, and further understanding will lead to the development of strategies to eliminate latent infection. The human gammaherpesvirus Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also referred to as human herpesvirus 8 (HHV-8), is an oncogenic virus etiologically associated with KS, primary effusion B-cell lymphoma (PEL) or body cavity B-cell lymphoma (BCBL), and plasmablastic multicentric Castleman's disease (pMCD) (1-3). In vivo, KSHV DNA and transcripts have been identified in human B cells, endothelial cells, epithelial cells, macrophages, and keratinocytes (3, 4). Similar to other herpesviruses, KSHV undergoes two distinguishable phases in its life cycle: latent and lytic infection (3, 4). During primary infection, KSHV initially establishes latent infection in specific target cells, during which multiple copies of the viral genome are stably maintained as extrachromosomal episomes (3,5). Only a few viral genes, primarily localized in the major latency locus of the genome, are expressed during this phase. These gene products bestow numerous essential functionalities to the dormant viral genome, such as evading host immune surveillance (6), promoting cellular proliferation (7-9), maintaining the viral episome (10), and tightly suppressing viral lytic gene expression (11). However, both spontaneous reactivation and induced reactivation of the latent genome occur, resulting in the systematic expression of the full repertoire of viral genes, which leads to viral genome replication and virion production (4). Previous studies suggested that lytic reactivation

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Section: Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

Nuclear Innate Immune DNA Sensor IFI16 Is Degraded during Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus (KSHV): Role of IFI16 in Maintenance of KSHV Latency

Roy

Dutta

Iqbal

et al. 2016

J Virol

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“…Previous studies demonstrated that neamine could inhibit the proliferation of human hepatoma H7402 cells (20) and human oral cancer HSC-2 cells (21). Furthermore, it suppressed the growth of the established A549 (22) HT-29, MDA-MB-435, A431 (23), HSC-2 and SAS (21) tumor transplants, and the formation of Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma (12).…”

Section: Introductionmentioning

confidence: 99%

“…Angiogenin can transfer to the nucleus to stimulate rRNA transcription, which is an indispensable process in angiogenesis and cell proliferation pathways, and is also a crossroad for angiogenesis induced by acidic and basic FGFs (αFGF, βFGF), VEGF and epidermal growth factor (10,11). In addition, angiogenin was reported to have an anti-apoptotic effect by targeting p53 and B-cell lymphoma 2, thereby accelerating cancer development (12). Angiogenin is upregulated in a number of cancers, including prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Neamine is preferential as an anti-prostate cancer reagent by inhibiting cell proliferation and angiogenesis, with lower toxicity than cis-platinum

Liu

2015

Oncology Letters

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Abstract. Hormone therapy is the most commonly used treatment for prostate cancer, but for androgen-independent cancer, few effective treatment methods are available. Therefore, the requirement to develop novel and effective anti-prostate cancer drugs is extremely urgent. Angiogenin has been suggested as a molecular target for prostate cancer treatment; its overexpression contributes to androgen-dependent prostate cancer growth and castration-resistant growth of androgen-independent prostate cancer. The aim of the present study was to investigate whether neamine, a low toxicity angiogenin nuclear translocation inhibitor, has preferential anti-prostate cancer activity compared with cis-platinum (DDP) and the mechanisms involved. Immunofluorescence and MTT assays were used to observe the effect of neamine on the nuclear translocation of angiogenin and cell proliferation, and a PC-3 cell transplanted tumor model was used to investigate the in vivo activity of neamine and DDP. Immunohistochemistry was performed to observe the expression of angiogenin, cluster of differentiation (CD)31 and Ki-67. It was found that neamine blocked nuclear translocation of angiogenin effectively and inhibited angiogenin-induced human umbilical vein endothelial cell and PC-3 cell proliferation in a dose-dependent manner. Neamine exerted a comparative antitumor effect, but lower toxicity (weight loss), in the PC-3 xenograft models treated with DDP. Neamine consistently reduced the expression of angiogenin and CD31 significantly, but no difference was found in Ki-67 expression compared with DDP. These data suggested that neamine may be a promising agent for prostate cancer treatment. IntroductionProstate cancer is the most prevalent malignancy and the second leading cause of cancer-related mortality in men worldwide (1). A total of 233,000 new cases and 29,480 associated mortalities are projected to occur in the United States in 2014 (2). Current therapy strategies for prostate cancer mainly include radical prostatectomy, external beam radiation, cryotherapy, chemotherapy or hormonal therapy. Among these, hormonal therapy is the most commonly used method, while for androgen-independent cancer, few effective treatment methods are available (3). Therefore, the requirement to develop novel and effective anti-prostate cancer drugs is extremely urgent.Angiogenesis is an essential step for the formation, progression and metastasis of numerous types of cancer, including prostate cancer (4). Previous studies have reported that the level of several angiogenic factors, such as vascular endothelial growth factor (VEGF) (5), transforming growth factor-β (6), fibroblast growth factors (FGFs) (7) and cyclooxygenase-2 (8), are upregulated in prostate cancer. An increasing number of studies are now focusing on angiogenin, a 14.4-kDa angiogenic ribonuclease, which was firstly isolated from the conditioned medium of human colon adenocarcinoma HT-29 cells based on its angiogenic activity, and which plays a controlling role in tumor angiogenesis (9). Angioge...

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“…It was reported that ANG targets p53 and B-cell lymphoma 2 to accelerate cancer development through anti-apoptotic effects [14]. Sheng et al explained a mechanism by which ANG stimulates rRNA transcription through an epigenetic activation of rDNA promotor [15].…”

Section: Introductionmentioning

confidence: 99%

A Novel Methodology for Structural, Functional and Toxicological Analysis of Mutant Angiogenin Protein in Human

Hassan¹,

Khan²,

Haidar³

et al. 2017

J Proteomics Bioinform

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Kaposi's Sarcoma-Associated Herpesvirus-Positive Primary Effusion Lymphoma Tumor Formation in NOD/SCID Mice Is Inhibited by Neomycin and Neamine Blocking Angiogenin's Nuclear Translocation

Cited by 24 publications

References 88 publications

Nuclear Innate Immune DNA Sensor IFI16 Is Degraded during Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus (KSHV): Role of IFI16 in Maintenance of KSHV Latency

Nuclear Innate Immune DNA Sensor IFI16 Is Degraded during Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus (KSHV): Role of IFI16 in Maintenance of KSHV Latency

Neamine is preferential as an anti-prostate cancer reagent by inhibiting cell proliferation and angiogenesis, with lower toxicity than cis-platinum

A Novel Methodology for Structural, Functional and Toxicological Analysis of Mutant Angiogenin Protein in Human

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