Abstract:
:Deregulation of cell survival pathways and resistance to apoptosis are widely accepted to be fundamental aspects of tumorigenesis. As in many tumours, the aberrant growth and survival of colorectal tumour cells is dependent upon a small number of highly activated signalling pathways, the inhibition of which elicits potent growth inhibitory or apoptotic responses in tumour cells. Accordingly, there is considerable interest in therapeutics that can modulate survival signalling pathways and target cancer cells for death. There is emerging evidence that cannabinoids, especially Delta(9)-tetrahydrocannabinol (THC), may represent novel anticancer agents, due to their ability to regulate signalling pathways critical for cell growth and survival. Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells. THC-induced apoptosis was rescued by pharmacological blockade of the CB1, but not CB2, cannabinoid receptor. Importantly, THC treatment resulted in CB1-mediated inhibition of both RAS-MAPK/ERK and PI3K-AKT survival signalling cascades; two key cell survival pathways frequently deregulated in colorectal tumours. The inhibition of ERK and AKT activity by THC was accompanied by activation of the proapoptotic BCL-2 family member BAD. Reduction of BAD protein expression by RNA interference rescued colorectal cancer cells from THC-induced apoptosis. These data suggest an important role for CB1 receptors and BAD in the regulation of apoptosis in colorectal cancer cells. The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Greenhough A,Patsos HA,Williams AC,Paraskeva Cdoi
10.1002/ijc.22917subject
Has Abstractpub_date
2007-11-15 00:00:00pages
2172-80issue
10eissn
0020-7136issn
1097-0215journal_volume
121pub_type
杂志文章abstract::Tumorigenic clonal lines derived from soft agar colonies induced by DMBA-transformed feline embryo cells were isolated and characterized. The morphologically altered clonal cells formed large aggregates, growing in this aggregate form when suspended in liquid growth medium above an agar base and forming colonies in so...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910280110
更新日期:1981-07-15 00:00:00
abstract::DNA repair is a complicated biological process, consisting of several distinct pathways, that plays a fundamental role in the maintenance of genomic integrity. The very important field of DNA repair and cancer risk has developed rapidly in the past decades. In this review of selected published data from our laboratory...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.24126
更新日期:2009-03-01 00:00:00
abstract::Loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) is a common event in many cancers and typically activates the maternally silenced allele. The resulting biallelic IGF2 expression correlates strongly with the hypomethylation of a differentially methylated region (DMR) near its promoter. It has also been ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25086
更新日期:2010-08-01 00:00:00
abstract::Azacytidine and decitabine are approved for treatment of acute myeloid leukemias and myelodysplastic syndromes. While clinical responses are attributed to epigenetic effects and induction of apoptosis in malignant cells, these azanucleosides also affect antitumor immune responses. NK cells as components of innate immu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25635
更新日期:2011-06-15 00:00:00
abstract::A segment of 712 bases coding for part of the human stearoyl-CoA desaturase gene was made by polymerase chain reaction (PCR) using primers based on published rat cDNA sequences. The human PCR product was confirmed by DNA sequencing. It was next cloned into a vector from which anti-sense, highly radioactive RNA transcr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910570310
更新日期:1994-05-01 00:00:00
abstract::G-protein-coupled receptor (GPCR)-stimulated androgen-independent activation of androgen receptor (AR) contributes to acquisition of a hormone-refractory phenotype by prostate cancer. We previously reported that regulator of G-protein signaling (RGS) 2, an inhibitor of GPCRs, inhibits androgen-independent AR activatio...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26138
更新日期:2012-04-01 00:00:00
abstract::Conventionally bred rats possess in their sera an NA which has a cytotoxic effect on a tumor cell line (KMT-17) derived from a fibrosarcoma induced by 3-methylcholanthrene and which can be absorbed by normal rat tissues. We have succeeded in purifying a glycosphingolipid as an antigen reactive to NA. GSLs isolated fro...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360613
更新日期:1985-12-15 00:00:00
abstract::Since most intracellular proteins are expressed with their ligands, ligands of cancer-testis (CT) antigens may also be CT in their distribution. Applying Sperm protein 17 (Sp17) as the bait in a yeast 2-hybrid system of a testicular cDNA library, 17 interacting clones were isolated and all encoded Ropporin, a spermato...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22842
更新日期:2007-10-01 00:00:00
abstract::The current paradigm stipulates that inhibition of histone deacetylase (HDAC) 6 is essential for the combinatorial effect of proteasome and HDAC inhibitors for the treatment of cancers. Our study aims to investigate the effect of combining different class I HDAC inhibitors (without HDAC6 action) with a proteasome inhi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28924
更新日期:2014-12-15 00:00:00
abstract::Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendri...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30002
更新日期:2016-06-01 00:00:00
abstract::Extensive hypermethylation and consecutive transcriptional silencing of tumorsuppressor genes have been documented in multiple tumor entities including breast cancer. In a microarray based genome-wide methylation analysis of five sporadic breast carcinomas we identified a hypermethylated CpG island within the first in...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22705
更新日期:2007-08-01 00:00:00
abstract::The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence,...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(20000715)87:2<295::aid-ijc23>3.0
更新日期:2000-07-15 00:00:00
abstract::Although tumor heterogeneity is widely accepted, the existence of cancer stem cells (CSCs) and their proposed role in tumor maintenance has always been challenged and remains a matter of debate. Recently, a path-breaking chapter was added to this saga when three independent groups reported the in vivo existence of CSC...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.28804
更新日期:2015-05-01 00:00:00
abstract::The emergence of mutations in the androgen receptor (AR) gene is a recurrent event during progression of prostate cancer (PCa) on androgen ablation therapy. In this study, we show that nonsense mutations that lead to carboxyl-terminal end truncated ARs are found at high frequency in metastatic PCas. Transcriptional ac...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22830
更新日期:2007-09-15 00:00:00
abstract::Nasopharyngeal carcinoma (NPC) is rare in most parts of the world, but prevalent in Southern China. Although this disease poses a serious health problem in our population, the genetic alterations that lead to the development of NPC have yet to be defined. In a comparative genomic hybridization (CGH) study on NPC by ou...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991029)83:3<305::aid-ijc
更新日期:1999-10-29 00:00:00
abstract::The association between Lichen planus (LP) and cancer has been under debate for decades. We studied the connection via population-based Finnish register data. All women with the diagnosis of LP (n = 13,100) were identified from the Finnish Hospital Discharge Registry from 1969-2012. These patients were linked with sub...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31025
更新日期:2018-01-01 00:00:00
abstract::In the past, it has been impossible to carry out immunohistological staining as part of a rapid histopathological diagnosis during surgery because the available methods were too time-consuming. The present report introduces a rapid indirect immunoperoxidase method that requires only 10-12 min. Thus, the immunological ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910350205
更新日期:1985-02-15 00:00:00
abstract::Human papillomavirus (HPV) genomes usually persist as episomal molecules in HPV associated preneoplastic lesions whereas they are frequently integrated into the host cell genome in HPV-related cancers cells. This suggests that malignant conversion of HPV-infected epithelia is linked to recombination of cellular and vi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::Biliary tract cancers have dismal prognoses even when cytotoxic chemotherapy is administered. There is an unmet need to develop precision treatment approaches using comprehensive genomic profiling. A total of 121 patients with biliary tract cancers were analyzed for circulating-tumor DNA (ctDNA) and/or tissue-based tu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.33230
更新日期:2021-02-01 00:00:00
abstract::Mammalian LIM kinase 1 (LIMK1) phosphorylates and inactivates the actin-binding and -depolymerizing factor cofilin and induces actin cytoskeletal changes. LIMK1 is reported to play an important role in cell motility, but the mechanism of induction of cell motility and the role of LIMK1 in tumor growth, angiogenesis an...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21650
更新日期:2006-06-01 00:00:00
abstract::Our previous clinicopathologic study revealed an inverse association of liver metastasis of colorectal cancer and stromal expression of matrix metalloproteinase-9 (MMP-9) or urokinase receptor (uPAR). This suggests that host cells, particularly macrophages, expressing matrix-degrading enzymes/factors could be protecti...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(20000401)86:1<24::aid-ijc4
更新日期:2000-04-01 00:00:00
abstract::Gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) have been shown to be associated with response to 5-fluorouracil-based therapies. Analyzing these gene expression levels in liver metastases is importan...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21692
更新日期:2006-08-01 00:00:00
abstract::To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0-14 years diagnosed with ALL between 1997 and 2002 from the population-based Cancer Registry of São Paulo, Brazil, covering 96 districts. Each child was assigned to an SES category based on the district of residence at dia...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23738
更新日期:2008-10-15 00:00:00
abstract::We have previously shown that anti-Ly-6C monoclonal antibody (MAb) 2B6-F2 identifies a subset of (CBA +/- C57BL/6)F1 splenic NK-1.1+ natural T (NT) cells which kill the NK-sensitive YAC-1 target in vitro. Furthermore, these Ly-6C+ cells are responsible for 40-50% of in vitro YAC-1 killing in all mouse strains tested. ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960516)66:4<532::AID-IJC
更新日期:1996-05-16 00:00:00
abstract::Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32045
更新日期:2019-05-01 00:00:00
abstract::RAGE is a central driver of tumorigenesis by sustaining an inflammatory tumor microenvironment. This study links the soluble forms of RAGE (sRAGE and esRAGE) with clinical outcome of melanoma patients. Moreover, tissue expression of RAGE was analyzed using immunohistochemistry on two independent tissue microarrays (TM...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29619
更新日期:2015-12-01 00:00:00
abstract::Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Tumor recurrence occurs in ∼20% of PTCs and some reach advanced stages. Promoter mutation in the telomerase reverse transcriptase (TERT) gene is identified to be a prognostic marker in PTC. However, the contribution of TERT promoter mutation ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31225
更新日期:2018-05-15 00:00:00
abstract::A series of 722 lung carcinomas, surgically resected and typed some years ago according to the 1967 WHO classification, was independently reviewed by 2 observers in order to test the reproducibility of histopathological typing when using the criteria of the 1981 WHO classification. Typing was fully agreed upon in 87% ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910530205
更新日期:1993-01-21 00:00:00
abstract::In order to study the mechanisms responsible for resistance to CDDP, 5 human tumor cell lines were made resistant to CDDP by repeated in vitro exposures. After cloning it was found that the cell lines developed were between 3.3-fold and 17-fold more resistant to CDDP than the parental cell lines at the IC90. These lin...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910470214
更新日期:1991-01-21 00:00:00
abstract::We found that rhabdomyosarcoma (RMS) subcellular membranes contain sialyltransferase activities for LcOse4Cer and GgOse4Cer acceptors. Chromatographic analyses and neuraminidase lability of the sialyltransferase products indicated that the principal site of sialylation was the non-reducing terminal galactosyl moiety. ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910450531
更新日期:1990-05-15 00:00:00