Abstract:
:Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that selectively induces apoptosis in several different types of human cancer cells. However, the potential use of LfcinB as an anticancer agent is presently limited by the need for relatively high concentrations of the peptide to trigger apoptosis. Ceramide is a membrane sphingolipid that is believed to function as a second messenger during apoptosis. In this study, we investigated the role of ceramide in LfcinB-induced apoptosis in CCRF-CEM and Jurkat T-leukemia cell lines. Exposure to LfcinB caused nuclear condensation and fragmentation, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation in CCRF-CEM and Jurkat T-cell acute lymphoblastic leukemia cell lines. Treatment with C6 ceramide, a cell-permeable, short-chain ceramide analog, also induced apoptotic nuclear morphology, PARP cleavage, and DNA fragmentation in T-leukemia cells. Although LfcinB treatment did not cause ceramide to accumulate in CCRF-CEM or Jurkat cells, the addition of C6 ceramide to LfcinB-treated T-leukemia cells resulted in increased DNA fragmentation. Furthermore, modulation of cellular ceramide metabolism either by inhibiting ceramidases with D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol or N-oleoylethanolamine, or by blocking glucosylceramide synthase activity with 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, enhanced the ability of LfcinB to trigger apoptosis in both Jurkat and CCRF-CEM cells. In addition, LfcinB-induced apoptosis of T-leukemia cells was enhanced in the presence of the antiestrogen tamoxifen, which has multiple effects on cancer cells, including inhibition of glucosylceramide synthase activity. We conclude that manipulation of cellular ceramide levels in combination with LfcinB therapy warrants further investigation as a novel strategy for the treatment of T cell-derived leukemias.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Furlong SJ,Ridgway ND,Hoskin DWsubject
Has Abstractpub_date
2008-03-01 00:00:00pages
537-44issue
3eissn
1019-6439issn
1791-2423journal_volume
32pub_type
杂志文章abstract::Cowden's disease (CD) is an autosomal dominant disorder which confers a high susceptibility to diverse benign and malignant tumors. The PTEN (phosphatase and tensin homologue deleted in chromosome ten) gene has been identified as a tumor suppressor gene responsible for cancers of the endometrium, ovary, prostate, and ...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.18.5.1017
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abstract::Glutathione S-transferase (GST) enzymes catalyse the detoxification of by-products of reactive oxygen species and are thus important in cellular defence mechanisms. The GSTs are polymorphic with allelic variants encoding isoforms with functional differences. GST polymorphism has been associated with susceptibility and...
journal_title:International journal of oncology
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doi:
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abstract::Changes in the expression of the putative p53-inducible inhibitor p21 of cyclin-dependent kinase (CDK) and p21-associated CDK activity were examined in relation to the DNA synthesis-associated nuclear exclusion of p53 after stimulating growth arrested human breast cancer MCF7 cells with serum. Following stimulation, p...
journal_title:International journal of oncology
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abstract::Alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of a heterologous gene. Alphavirus vectors, Semliki Forest virus (SFV), Sindbis virus (SIN) and Venezuelan equine encephalitis virus (VEE) have been developed as gene expression vecto...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
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更新日期:2004-04-01 00:00:00
abstract::The tumour suppressor gene hypermethylated in cancer 1 (HIC1) is a transcriptional repressor, which functionally cooperates with p53. Loss of HIC1 function is associated with the development of various tumor entities. The aim of this study was to elucidate the relevance of CpG islan...
journal_title:International journal of oncology
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abstract::Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of histone deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression patterns and biological role of HDAC3 in pancreatic cancer remain unclear. I...
journal_title:International journal of oncology
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doi:10.3892/ijo.2014.2568
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::Clinical trials using antiangiogenic drugs revealed their potential against cancer. Unfortunately, a large percentage of patients does not yet benefit from this therapeutic approach highlighting the need of diagnostic tools to non-invasively evaluate and monitor response to therapy. It would also allow to predict whic...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2016.3553
更新日期:2016-08-01 00:00:00
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journal_title:International journal of oncology
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更新日期:2010-02-01 00:00:00
abstract::Point mutations in the K-ras gene are observed at a high incidence in human pancreatic carcinomas. These alterations can be used as potential targets for specific ribozyme-mediated reversal of the malignant phenotype. We designed an anti-K-ras ribozyme against codon 12 of the mutant K-ras gene transcripts (GGT right c...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::Glioblastomas are highly vascularized tumors and anti-angiogenic strategy is one of the most promising therapeutic approaches to treat brain tumors. Interferon alpha (IFN-alpha) as a single agent or combined with standard chemo-therapy has been shown to inhibit various tumors, but the effect of combination anti-angiog...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-06-01 00:00:00
abstract::Serum ferritin is elevated in many cancers. Using the subtraction-enhanced display technique, we isolated several cDNA clones including ferritin-H which is overexpressed in rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine. We investigated hepatic messenger RNA (mRNA) levels of ferritin-H in patients wi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.1.187
更新日期:1997-07-01 00:00:00
abstract::We investigated the clinical significance of the expression levels of matrix metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on inhibiting proliferation and invasion of RCC. We evaluated the expression levels of MMP-...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2073
更新日期:2013-11-01 00:00:00
abstract::Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study w...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2657
更新日期:2014-12-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2019-03-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.6.1075
更新日期:1999-06-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2010-12-01 00:00:00
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journal_title:International journal of oncology
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doi:
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journal_title:International journal of oncology
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doi:
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::A murine B16 melanoma parental line (B16) and two clones either pigmented (B16P) or non-pigmented (B16NP) were cocultured as aggregates with mouse 3T3 fibroblasts. In vivo, these mixed aggregates developed more aggressive tumors in the mouse than corresponding pure aggregates. In vitro, the three pure cell lines secre...
journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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pub_type: 杂志文章
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