Abstract:
:Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to extend their biological activity. Previous studies have indicate an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group, and that using inhibitors of the mevalonate pathway could block the transforming properties of ras oncogene. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we partially purified farnesyl protein transferase (FPTase) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro from porcine kidney epithelial-like LLC-PK 1 cells, human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells. This FPTase activity requires a divalent cation, such as Mg2+ or Zn2+ ions, sulfhydryl protecting agent, DTT, as well as certain pH which is linear with time and with enzyme concentration, and is present in many mammalian normal cell and tumor cell lines. Sequentially, we observed the effects of the monoterpene compound, d-limonene; curcumin derivatives, CD-I and CD-II; polyphenol compound, gallotannin; Salvia miltiorrhiza derivative, SMD; and retinoid acid derivative, RAD on FPTase activity. We found that curcumin derivatives and gallotannin had a strong inhibition on FPTase besides d-limonene, while gallotannin was the strongest among synthetic and natural compounds tested. Salivia miltiorrhiza and retinoid acid derivatives had no influence on FPTase activity. Our results suggest that compounds containing polyphenol hydroxyl may be a new source of FPTase inhibitors. The experiment also showed that availability of an in vitro farnesyl protein transferase assay could be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Chen X,Hasuma T,Yano Y,Yoshimata T,Morishima Y,Wang Y,Otani Ssubject
Has Abstractpub_date
1997-07-01 00:00:00pages
2555-64issue
4Aeissn
0250-7005issn
1791-7530journal_volume
17pub_type
杂志文章abstract:BACKGROUND:Aberrant methylation of tumor suppressor gene (TSG) promoters has been extensively investigated in nasopharyngeal carcinomas (NPC) from South East Asia but not from North Africa. PATIENTS AND METHODS:The methylation status of p16, deleted in lung and esophageal cancer (DLEC1), zinc finger, MYND-type contain...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-07-01 00:00:00
abstract::Radiomics, an emerging field in radiation therapy, is hypothesized to improve classification of tumour risk and prognosis. Despite encouraging results, there are issues of practicality and interpretation of radiomic data. This study investigates the emerging role of radiomics in tumour risk classification and prognosi...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:10.21873/anticanres.14350
更新日期:2020-07-01 00:00:00
abstract::D-Penicillamine, a structural analog of cysteine, has the ability to chelate metal ions and reacts with cysteine. We have shown earlier that D-Penicillamin is a potential inhibitor of tat-mediated transactivation of HIV-1-LTR (14) and possesses anti-HIV-1 activity (23). Following this approach, we evaluated the anti-t...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Mistletoe lectins (MLs) are the active components of aqueous mistletoe extracts widely used in complementary cancer therapy, however, it is not clear if they bind to carbohydrate residues only or whether they interact with proteins as well. Protein-protein interactions do not seem unlikely as MLs act at very...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2009-12-01 00:00:00
abstract::Moxa smoke induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in other cell lines. The cytotoxic activity of Moxa smoke was significantly reduced by a popular antioxidant, N-acetyl-L-cysteine (NAC). Moxa smoke showed oxidation potential (measured by NO monitor) and produced...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:The aim of this study was to investigate the effect of breast cancer adjuvant therapies on the levels of circulating surfactant protein-D (SP-D), C-Reactive protein (CRP) and soluble receptor for advanced glycation end-products (sRAGE), as potential biomarkers of subclinical pulmonary inflammation. MATERIAL...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-11-01 00:00:00
abstract::The recombinant plasmid pBHIV-1 carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1), linked to the reported chloramphenicol acetyl transferase (CAT) gene, was introduced into human and rat fibroblasts. Stable transfectants were obtained which were resistant to genetecin and expressed ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:Recent experimental studies have indicated that cyclooxygenase-2 (COX-2) suppresses tumor-cell apoptosis and induces intratumoral angiogenesis. PATIENTS AND METHODS:A series of 70 endometrial cancer cases that had undergone a curative resection was studied to determine the correlation between COX-2 expressi...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2007-11-01 00:00:00
abstract::Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Adrenocortical Carcinoma (ACC) is rare with an annual incidence of 0.5-2 cases per million worldwide. Some ACC tumors over express N-cadherin, which correlates with metastatic potential. ADH-1 (Exherin™) is a competitive inhibitor of N-cadherin, resulting in rapid onset of tumor vascular angiolysis and apoptosis in pr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2011-11-01 00:00:00
abstract::The antitumor effects of the somatostatin structural derivative TT-232 in different rodent and xenograft tumor models are summarized in this report. TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Since the anti-HER2 monoclonal antibody trastuzumab made its triumphant advance into breast cancer therapy, new selective agents, including pan-HER inhibitors are entering clinical practice. MATERIALS AND METHODS:This study investigates the expression of the four HER-family members, HER1-4, in 48 primary br...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
abstract::A significant number of human tumors from diverse histological origins contain c-K-ras oncogenes which have been activated by somatic point mutations resulting in single amino acids substitutions in the encoded p21 ras protein. In addition to these qualitative changes, other genetic alterations leading to increased ex...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:1987-07-01 00:00:00
abstract::Long-term results of different studies employing cisplatin-based chemotherapy in advanced ovara in cancer are just beginning to be published. Available data suggest that the rate of relapse decreases but does not cease, and the question of whether cisplatin-based chemotherapy results in an improved cure in advanced ov...
journal_title:Anticancer research
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1989-11-01 00:00:00
abstract:OBJECTIVES:To investigate the roles of insulin-like growth factor II (IGF2), myeloperoxidase (MPO), E-cadherin (CDH1), urokinase and xeroderma pigmentosum group A and D (XPA, XPD) polymorphisms upon leiomyoma susceptibility. STUDY DESIGN:Women were divided into: group 1, leiomyoma (n=158); group 2, non-leiomyoma (n=15...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:In vitro studies have indicated that epidermal growth factor receptor (EGFR) may intensify signaling output by the receptor's overexpression, heterodimerization with HER-2, or autocrine expression of ligands. The purpose of the present study was to evaluate the correlation between EGFR and its related protei...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND/AIM:Elderly patients with HPV+ oropharyngeal cancer (OPC) represent an understudied cohort of the HPV epidemic. We aimed to investigate the clinical presentation, treatment tolerability and outcomes in patient's ≥65 years old with HPV+ OPC. PATIENTS AND METHODS:We identified all patients aged 65 and older t...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.11520
更新日期:2017-04-01 00:00:00
abstract::Glioblastomas are the most frequent and most malignant astrocytic gliomas. The epidermal growth factor receptor (EGFR) gene is the most frequently amplified and overexpressed in glioblastomas. The expression of bcl-2 and Bax in EGFR-antisense transfected and un-transfected glioblastoma cell line, U87E and U87V was stu...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::VEGF is an important angiogenic cytokine with a critical role in tumor angiogenesis. VEGF concentrations were measured using an ELISA assay, detecting VEGF165 isoform, in tumor cyst and/or ascitic fluids and in sera of 86 patients with malignant neoplasms and in 53 patients with benign ovarian neoplasms. VEGF levels w...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::The continuity of the subepithelial band of lamina propria-indigenous macrophages (SBLP-M) discourages commensal gut bacteria from invading the host. In this Review we analyzed the impact of a disintegrating SBLP-M in inflammatory bowel disease (IBD), which results in microbiota inflow, inadequate immune responses and...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:10.21873/anticanres.12664
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND/AIM:Lobarstin is a metabolite occurring from the Antarctic lichen Stereocaulon alpnum. Human glioblastoma is highly resistant to chemotherapy with temozolomide. Lobarstin was examined for its effect on glioblastoma. MATERIALS AND METHODS:Temozolomide-resistant T98G cells were subjected to toxicity test with...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2013-12-01 00:00:00
abstract::AIDS-related Epstein-Barr virus (EBV)-associated T cell lymphomas are emerging as a new, distinct histopathological entity. The pathway whereby EBV infects T cells as well as the initial EBV transcriptional program in T cells has not been established. In order to shed light on the early events of the EBV infection of ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to determine the efficacy of a combination of gemcitabine and sirolimus in a mouse model of invasive bladder cancer. MATERIALS AND METHODS:Gemcitabine (50 mg/kg) and sirolimus (1.5 mg/kg) were administered to animals previously exposed to N-butyl-N-4(hydroxybutyl)nitrosamine in...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Calpains (CAPN) are intracellular, non-lysosomal cytoplasmic cysteine endopeptidases and they are expressed ubiquitously. Their endogenous specific inhibitor is calpastatin. When calcium is present, calpastatin and calpain attach to each other, inhibiting the protease. The calpain system plays an important r...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2010-07-01 00:00:00
abstract::We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::A possible influence of tamoxifen (TAM) treatment on the measurable content of some steroid hormone receptors (i.e. ER, PgR, AR) from primary breast cancers has been evaluated. In eleven postmenopausal women, two biopsies were taken from the same tumor, the first biopsy before starting endocrine treatment, and a secon...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::The effects of all-trans retinoic acid (ATRA), either alone or in combination with GM-CSF, on the induction of differentiation of a human myeloblastic leukemia cell line, ML-1, were investigated. ATRA alone caused only slight induction of NBT-reducing activity even at a high concentration (10(-7) M), but when combined...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::To determine the changes in biological features of the prostate during the course of local recurrence of prostate cancer after endocrine therapy, histologic grade, proliferating activity and apoptotic indices were examined in prostate specimens obtained before treatment and at recurrence. A total of 16 patients, who h...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract:BACKGROUND:Vitamin D is known for its anti-cancerogenous potential. Prostaglandin E2 (PGE2) is a proliferation and inflammation activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX-2). A link between vitamin D and PGE2 metabolism was recently shown. MATERIALS AND METHODS:In MD...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-02-01 00:00:00
abstract::We have previously reported the presence of human beta-defensin-2 (HBD-2), a peptide with antimicrobial and cytotoxic properties, in oral squamous cell carcinomas. The aim of the present study was to measure the concentration of HBD-2 in abnormal tissues such as oral squamous cell carcinomas. HBD-2 was extracted from ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00