Abstract:
BACKGROUND:The five-year survival rates for head and neck squamous cell carcinoma (HNSCC) patients are less than 50%, and the prognosis has not improved, despite advancements in standard multi-modality therapies. Hence major emphasis is being laid on identification of novel molecular targets and development of multi-targeted therapies. 14-3-3 zeta, a multifunctional phospho-serine/phospho-threonine binding protein, is emerging as an effector of pro-survival signaling by binding to several proteins involved in apoptosis (Bad, FKHRL1 and ASK1) and may serve as an appropriate target for head and neck cancer therapy. Herein, we determined effect of guggulsterone (GS), a farnesoid X receptor antagonist, on 14-3-3 zeta associated molecular pathways for abrogation of apoptosis in head and neck cancer cells. METHODS:Head and neck cancer cells were treated with guggulsterone (GS). Effect of GS-treatment was evaluated using cell viability (MTT) assay and apoptosis was verified by annexin V, DNA fragmentation and M30 CytoDeath antibody assay. Mechanism of GS-induced apoptosis was determined by western blotting and co-IP assays using specific antibodies. RESULTS:Using in vitro models of head and neck cancer, we showed 14-3-3 zeta as a key player regulating apoptosis in GS treated SCC4 cells. Treatment with GS releases BAD from the inhibitory action of 14-3-3 zeta in proliferating HNSCC cells by activating protein phosphatase 2A (PP2A). These events initiate the intrinsic mitochondrial pathway of apoptosis, as revealed by increased levels of cytochrome c in cytoplasmic extracts of GS-treated SCC4 cells. In addition, GS treatment significantly reduced the expression of anti-apoptotic proteins, Bcl-2, xIAP, Mcl1, survivin, cyclin D1 and c-myc, thus committing cells to apoptosis. These events were followed by activation of caspase 9, caspase 8 and caspase 3 leading to cleavage of its downstream target, poly-ADP-ribose phosphate (PARP). CONCLUSION:GS targets 14-3-3 zeta associated cellular pathways for reducing proliferation and inducing apoptosis in head and neck cancer cells, warranting its investigation for use in treatment of head and neck cancer.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Macha MA,Matta A,Chauhan S,Siu KM,Ralhan Rdoi
10.1186/1471-2407-10-655subject
Has Abstractpub_date
2010-11-30 00:00:00pages
655issn
1471-2407pii
1471-2407-10-655journal_volume
10pub_type
杂志文章相关文献
BMC CANCER文献大全abstract:BACKGROUND:Colorectal cancer is the second most common cause of cancer deaths for both men and women, and the third most common cause of cancer in the U.S. Toxicity of current chemotherapeutic agents for colorectal cancer, and emergence of drug resistance underscore the need to develop new, potentially less toxic alter...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-016-2861-5
更新日期:2016-12-08 00:00:00
abstract:BACKGROUND:Endometrial cancer, one of the most common malignant tumors, is a serious threat to women's health. Endometrial hyperplasia is a precursor of endometrial cancer. S100 calcium binding protein P (S100P) has been found to play important roles in many types of cancer. The present study aimed to investigate the e...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07350-x
更新日期:2020-09-03 00:00:00
abstract:BACKGROUND:The glycosylphosphatidylinositol-anchored extracellular membrane serine protease prostasin is expressed in normal bladder urothelial cells. Bladder inflammation reduces prostasin expression and a loss of prostasin expression is associated with epithelial-mesenchymal transition (EMT) in human bladder transiti...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-2039-6
更新日期:2015-12-29 00:00:00
abstract:BACKGROUND:The nucleic acid mutation status in intracranial metastasis is markedly significant clinically. The goal of the current study was to explore whether the tumor-associated mutations can be detected by different next-generation sequencing (NGS) pipelines in paired cerebrospinal fluid (CSF) and plasma samples fr...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-5348-3
更新日期:2019-02-12 00:00:00
abstract:BACKGROUND:Colorectal cancer screening is key to early detection and thus to early treatment, but uptake is often sub-optimal, particularly amongst lower income groups. It is proposed that the imminent introduction of the single-sample Faecal Immunochemical Test (FIT) in Scotland may lead to increased uptake as compare...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-016-2133-4
更新日期:2016-02-13 00:00:00
abstract:BACKGROUND:Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenv...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4180-5
更新日期:2018-03-09 00:00:00
abstract:BACKGROUND:Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival), combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®). Radiation the...
journal_title:BMC cancer
pub_type: 杂志文章,多中心研究
doi:10.1186/1471-2407-10-651
更新日期:2010-11-26 00:00:00
abstract:BACKGROUND:Disorders of cell adhesion are critical steps in cancer progression in which varieties of markers including cadherins are involved in.Btbd7 was found to inhibit E-cadherin expression in MDCK cells and play important roles during branching morphogenesis of embryonic salivary glands and lungs. However its func...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-704
更新日期:2014-09-24 00:00:00
abstract:BACKGROUND:UroVysion fluorescence in situ hybridization (uFISH) was reported to have superior sensitivity to urine cytology. However uFISH studies are limited by varying definitions of what is considered a positive result, absence of histopathology and small sample size. The aim of our study was to better determine the...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3227-3
更新日期:2017-04-07 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) is a disease that can be prevented through early detection. Through the use of effective educational tools, individuals can become better informed about CRC and understand the importance of screening and early detection. The walk through Inflatable Colon is an innovative educational r...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-626
更新日期:2014-08-28 00:00:00
abstract:BACKGROUNDS:Cancer stem cell (CSC) research has highlighted the necessity of developing drugs targeting CSCs. We investigated a hepatocellular carcinoma (HCC) cell line that not only has CSC hierarchy but also shows phenotypic changes (population changes) upon differentiation of CSC during culture and can be used for s...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1297-7
更新日期:2015-04-11 00:00:00
abstract:BACKGROUND:The aim of the study was to investigate whether p503S, p504S and p510S gene expression in peripheral-blood be useful as a diagnostic or prognostic marker of prostatic cancer. METHODS:Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect p503S, p504S and p510...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-5-111
更新日期:2005-09-05 00:00:00
abstract:BACKGROUND:Neuroendocrine tumors (NETs) of the esophagus are extremely rare, and few cases have been reported worldwide. Thus, a comprehensive nationwide study is needed to understand the characteristics of and treatment strategy for esophageal NETs. METHODS:We collected data on esophageal NET patients from 25 hospita...
journal_title:BMC cancer
pub_type: 杂志文章,多中心研究
doi:10.1186/1471-2407-14-569
更新日期:2014-08-07 00:00:00
abstract:BACKGROUND:Infection with human papillomavirus (HPV) is necessary for the development of cervical carcinoma. By contrast, the role of HPV in the pathogenesis of other malignancies, such as head and neck cancers, is less well characterised. This study aimed to address key information gaps by conducting a systematic revi...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1471-2407-14-968
更新日期:2014-12-17 00:00:00
abstract:BACKGROUND:Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-relate...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-9-296
更新日期:2009-08-24 00:00:00
abstract:BACKGROUND:We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker. METHODS:Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3209-5
更新日期:2017-03-23 00:00:00
abstract:BACKGROUND:A low cost and accurate method for detecting high-risk (HR) human papillomavirus (HPV) is important to permit HPV testing for cervical cancer prevention. We used a commercially available HPV method (H13, Hybribio) which was documented to function accurately in a reduced volume of cervical specimen to determi...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4438-y
更新日期:2018-05-15 00:00:00
abstract:BACKGROUND:Single-cell mRNA profiling of circulating tumour cells may contribute to a better understanding of the biology of these cells and their role in the metastatic process. In addition, such analyses may reveal new knowledge about the mechanisms underlying chemotherapy resistance and tumour progression in patient...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3385-3
更新日期:2017-05-31 00:00:00
abstract:BACKGROUND:Unilateral weakness of an upper extremity is most frequently caused by traumatic nerve injury or compression neuropathy. In rare cases, lesion of the central nervous system may result in syndromes suggesting peripheral nerve damage by the initial examination. Pseudoperipheral hand palsy is the best known of ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4857-9
更新日期:2018-10-03 00:00:00
abstract:BACKGROUND:To evaluate the effect of Recurrence Score® results (RS; Oncotype DX® multigene assay ODX) on treatment recommendations by Swiss multidisciplinary tumor boards (TB). METHODS:SAKK 26/10 is a multicenter, prospective cohort study of early breast cancer patients: Eligibility: R0-resection, ≥10% ER+ malignant c...
journal_title:BMC cancer
pub_type: 杂志文章,多中心研究
doi:10.1186/s12885-017-3261-1
更新日期:2017-04-13 00:00:00
abstract:BACKGROUND:Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Sever...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-253
更新日期:2014-04-11 00:00:00
abstract:BACKGROUND:Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobac...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-8-310
更新日期:2008-10-27 00:00:00
abstract:BACKGROUND:Standard chemotherapy in unresectable biliary tract carcinoma (BTC) patients is based on gemcitabine combined with platinum derivatives. However, primary or acquired resistance is inevitable and no second-line chemotherapy is demonstrated to be effective. Thus, there is an urgent need to identify new alterna...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-918
更新日期:2014-12-05 00:00:00
abstract:BACKGROUND:Cancer metastasis and drug resistance have traditionally been studied separately, though these two lethal pathological phenomena almost always occur concurrently. Brain metastasis occurs in a large proportion of lung cancer patients (~ 30%). Once diagnosed, patients have a poor prognosis surviving typically ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-06808-2
更新日期:2020-04-07 00:00:00
abstract:BACKGROUND:FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, an...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-11-38
更新日期:2011-01-27 00:00:00
abstract:BACKGROUND:Socioeconomic inequalities in cancer mortality in Britain have been shown to be present in the 1990s and early 2000s. Little is known about on-going patterns in such inequalities in cancer mortality. We examined time trends in socioeconomic inequalities in cancer mortality in Britain between 1978 and 2013. ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-474
更新日期:2014-06-30 00:00:00
abstract::It has been highlighted that the original manuscript [1] contains a typesetting error in the surname of Jesson Butcon. This was incorrectly captured as Jessica Butcon in the original manuscript which has since been updated. ...
journal_title:BMC cancer
pub_type: 杂志文章,已发布勘误
doi:10.1186/s12885-018-4105-3
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Data concerning incidence and prevalence of cancer in the different regions of Russia have traditionally not been provided on a basis that facilitated comparison with data from countries in western parts of Europe. The oncological hospital in Arkhangelsk, in co-operation with Universitetet i Tromsø (Norway),...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-5-82
更新日期:2005-07-19 00:00:00
abstract:BACKGROUND:KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the func...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-194
更新日期:2014-03-15 00:00:00
abstract:BACKGROUND:Uridine 5'-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3463-6
更新日期:2017-07-03 00:00:00