Sulindac and its metabolites inhibit invasion of glioblastoma cells via down‐regulation of Akt/PKB and MMP‐2

Lee, Hyung-Chahn; Park, In-Chul; Park, Jong Bae; An, Sungkwan; Woo, Sang-Hyeok; Jin, Hyeon‐Ok; Chung, Hee Yong; Lee, Su‐Jae; Gwak, Ho-Shin; Hong, Young-Jun; Yoo, Doo-Hyun; Rhee, Chang-Hun; Hong, Seok‐Il

doi:10.1002/jcb.20312

Cited by 48 publications

(35 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6). 20,38 Interestingly, Joy et al demonstrated that migrating glioblastoma cells become more resistant to apoptosis than migration-restricted cells. This suggests that identifying therapeutics that inhibit glioblastoma migration and invasion may be important in sensitizing glioblastoma to apoptosis.…”

Section: Embryo-larval Zebrafish Xenograft Assay 325mentioning

confidence: 99%

Developing a Novel Embryo–Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

et al. 2016

View full text Add to dashboard Cite

Glioblastoma is an aggressive brain cancer requiring improved treatments. Existing methods of drug discovery and development require years before new therapeutics become available to patients. Zebrafish xenograft models hold promise for prioritizing drug development. We have developed an embryo-larval zebrafish xenograft assay in which cancer cells are implanted in a brain microenvironment to discover and prioritize compounds that impact glioblastoma proliferation, migration, and invasion. We illustrate the utility of our assay by evaluating the well-studied, phosphatidylinositide 3-kinase inhibitor LY294002 and zinc oxide nanoparticles (ZnO NPs), which demonstrate selective cancer cytotoxicity in cell culture, but the in vivo effectiveness has not been established. Exposures of 3.125-6.25 lM LY294002 significantly decreased proliferation up to 34% with concentration-dependent trends. Exposure to 6.25 lM LY294002 significantly inhibited migration/invasion by *27% within the glioblastoma cell mass (0-80 lm) and by *32% in the next distance region (81-160 lm). Unexpectedly, ZnO enhanced glioblastoma proliferation by *19% and migration/invasion by *35% at the periphery of the cell mass (161+ lm); however, dissolution of these NPs make it difficult to discern whether this was a nano or ionic effect. These results demonstrate that we have a short, relevant, and sensitive zebrafishbased assay to aid glioblastoma therapeutic development.

show abstract

Section: Embryo-larval Zebrafish Xenograft Assay 325mentioning

confidence: 99%

Developing a Novel Embryo–Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Other studies demonstrated that celecoxib and sulindac exerted antiangiogenic effects by inhibiting proliferation of human umbilical vein endothelial cells, 86 and by inhibiting activities of other proangiogenic factors, such as matrix metalloprotease 2 and 9, and the early growth response factor Egr-1. [87][88][89] Aspirin, at therapeutic concentrations, was found to inhibit tube formation in a 3-dimensional collagen angiogenesis model, via a COX-independent mechanism, which may contribute to its cancer chemoprotective effects. 90 The question of exactly how statins and NSAIDs work in a synergistic fashion to produce enhanced anticarcinogenic effects is largely unresolved.…”

Section: Mechanisms Of Actionsmentioning

confidence: 99%

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

Xiao

Yang

2008

Intl Journal of Cancer

View full text Add to dashboard Cite

Statins and nonsteroidal antiinflammatory drugs (NSAIDs) are commonly prescribed for lowering cholesterol and antiinflammation, respectively. Recently, their potential roles as cancer chemopreventive agents have been subject to intensive studies. Human trials have not provided conclusive results on the protective effects of statins against different cancers, while more convincing results have been observed for cancer preventive effects of NSAIDs, especially on colorectal cancer. A promising strategy to enhance the cancer preventive efficacy of statins and NSAIDs is to use them in combination, which may produce synergy and lower the dose required for each agent. This strategy is of particular interest for potential use of low doses of statins and NSAIDs on a long-term basis for cancer chemoprevention; increased risks for gastrointestinal and cardiovascular side effects associated with the use of NSAIDs have been observed in colorectal cancer chemopreventive trials. This article reviews the evidence for the cancer preventive actions of statins and NSAIDs, as well as their possible synergistic action and the mechanisms involved. ' 2008 Wiley-Liss, Inc.Key words: statins; NSAIDs; cancer chemoprevention While the mortality from major chronic diseases, such as cardiovascular and cerebrovascular diseases, has decreased substantially during the past half century in the United States, the mortality from cancer has just begun to show a slight decrease. Cancer has become the number one killer of both men and women under age 85 years in the United States.1 A promising approach to controlling cancer is to prevent it before malignant events have occurred.2 Cancer chemoprevention refers to the use of natural or synthetic substances to inhibit, retard or reverse the carcinogenesis.3 A wealth of evidence from preclinical studies have convincingly demonstrated the cancer preventive efficacy of various agents in different animal models. However, the data from observational, case-control, cohort studies, and randomized trials in humans have overall demonstrated mixed results. Statins and nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to be potential cancer chemopreventive agents. This review focuses on an attractive approach of chemoprevention using the combination of statins and NSAIDs. Statin and cancer chemopreventionStatins are small-molecule inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which are widely used as cholesterol-lowering drugs. Besides their use in the treatment of lipid disorders, statins have showed anticarcinogenic activities in many in vitro and in vivo preclinical studies, and attracted much attention in exploring their roles in cancer chemoprevention. Several observational human studies reported potential protective effects of statin use against overall risk of cancer, 4-6 whereas other studies did not 7,8 (Table I). In a case-control study in Quebec, Canada, statin use was found to be associated with a 28% reduction in the risk of developing cancer (RR 5 0.72, 95% ...

show abstract

“…It has been shown that NSAIDs can induce activation of PTEN and other phosphatases [19], or inhibit Akt kinase activity [20,21].…”

Section: Authors and Affiliationsmentioning

confidence: 99%

“…Interestingly, one of the prostaglandin-independent mechanisms of NSAIDs action could be inhibition of the PI3K/PKB/Akt pathway. It has been shown that higher doses of NSAIDs can induce activation of PTEN and other phosphatases [19], or inhibit Akt kinase activity [20,21]. In mammals, three Akt isoforms are expressed, Akt1/PKB, Akt2/PKB, and Akt3/PKB [41].…”

Section: Reduction Of Ship2 Expression Leads To Sensitisation Of Cellmentioning

confidence: 99%

Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs

Lincová¹,

Hampl²,

Pernicová³

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 42A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 1 Full-length Research PaperClassification: Antibiotics and Chemotherapeutics Title:Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs Authors and affiliations:Eva 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractAntitumorigenic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are well established in several types of cancer disease. However, the mechanisms driving these processes are not understood in all details. In our study, we observed significant differences in sensitivity of cancer epithelial cell lines to COX-independent antiproliferative effects of NSAIDs. The prostate cancer cell line LNCaP, lacking both critical enzymes in the negative control of PKB/Akt activation, PTEN and SHIP2, was the most sensitive to these effects, as assessed by analysing the cell cycle profile and expression of cell cycle regulating proteins. We found that p53 protein and its signalling pathway is not involved in early antiproliferative action of the selected NSAID -indomethacin. RNAi provided evidence for involvement of p21 increased sensitivity to chemopreventive effects of these widely used drugs.

show abstract

Sulindac and its metabolites inhibit invasion of glioblastoma cells via down‐regulation of Akt/PKB and MMP‐2

Cited by 48 publications

References 49 publications

Developing a Novel Embryo–Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

Developing a Novel Embryo–Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

Multiple defects in negative regulation of the PKB/Akt pathway sensitise human cancer cells to the antiproliferative effect of non-steroidal anti-inflammatory drugs

Contact Info

Product

Resources

About