Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells

Yu, Honggang; Huang, Jie-An; Yang, Yanning; Luo, Haitao; Yu, Jie-Ping; Meier, Juris J.; Schrader, Henning; Bastian, Andreas; Schmidt, Wolfgang E.; Schmitz, Frank

doi:10.1016/s0167-0115(03)00084-3

Cited by 15 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is evident that arachidonic acid and PGE2 are anti-apoptotic effects in various cancer cells and chemical-induced carcinogenesis in animal models [27], confirming our data obtained in the present study. In addition, cPLA2 is cleaved by caspase-3 and/or a related caspase in cells undergoing apoptosis [1,33]. As a consequence, the activated caspase-3 might be involved in the cleavage of cPLA2, leading to lower arachidonic acid content and PGE2 contents with response to the lowered COX-2 protein level in A-549 cells treated with β-ionone.…”

Section: Expression or Activation Of Anti-apoptotic Proteins On A-549mentioning

confidence: 99%

Anti-proliferative Effects of β-ionone on Human Lung Cancer A-549 Cells

Lee¹,

Kim²,

Jang³

et al. 2013

Journal of Life Science

View full text Add to dashboard Cite

The anti-proliferative activity of β-ionone was investigated on human non-small lung cancer A-549 cells (designated A-549 cells). A-549 cells were treated with various concentrations of β-ionone (1, 5, 10, and 15 μM) for two, four, and six days. Biochemical markers related to the growth inhibition of A-549 cells by β-ionone were measured at the second day of incubation. β-Ionone inhibited the growth of A-549 cells by dose-and time-dependent manners, resulting in an IC50 of 5.0 μg/ml at the second day of incubation. β-Ionone induced apoptosis by a dose-dependent manner. β-Ionone increased levels of p53, p21, and Bax proteins, but suppressed expression of the Bcl-2 protein. Similarly, β-ionone enhanced cytochrome c release from the mitochondria to the cytosol, and induced activation of caspase-9 and -3. Additionally, β-ion-one reduced cPLA2 and COX-2 protein levels. These results suggest that the β-ionone inhibits the proliferation of A-549 cells through reciprocal regulation of Bax and Bcl-2 gene expression and suppression of cPLA2 and COX-2 protein expressions.

show abstract

Section: Expression or Activation Of Anti-apoptotic Proteins On A-549mentioning

confidence: 99%

Anti-proliferative Effects of β-ionone on Human Lung Cancer A-549 Cells

Lee¹,

Kim²,

Jang³

et al. 2013

Journal of Life Science

View full text Add to dashboard Cite

show abstract

“…(9)], with a range of theories in circulation such as; cyclooxygenase (COX) inhibition (7,10), NF-κB inhibition (11)(12)(13), NF-κB activation (14,15), down-regulation of Bcl-2 expression (16,17), thus making the cells less resistant to the initiation of apoptosis, and down-regulation of c-Myc, cyclin D1, cyclin A and proliferating cell nuclear antigen (PCNA) (18), the intrinsic antioxidant activity of aspirin preventing double stranded DNA breaks (19), aspirin induces translocation of Bax to mitochondria (20), NSAIDSs up-regulate 15-lipoxygenase-1 expression (21), inhibition of cytosolic phospholipase A 2 expression (22), depletion of intracellular polyamines (23), increased Rac 1 expression (24), increased NSAID-activated gene (NAG-1) protein (25 and refs. therein), selection for microsatellite stability (26), and induction of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells, which ultimately facilitates programmed cell death (27).…”

Section: Introductionmentioning

confidence: 99%

Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line

Nicholl¹

2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. Regular aspirin intake is associated with a reduction in the incidence of colorectal cancer. Aspirin has been shown to be cytotoxic to colorectal cancer cells in vitro. The molecular basis for this cytotoxicity is controversial, with a number of competing hypotheses in circulation. One suggestion is that the protective effect is related to the induction of expression of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells. We report that treatment of the DNA MMR competent/p53 mutant colorectal cancer cell line SW480 with 1 mM aspirin for 48 h caused changes in mRNA expression of several key genes involved in DNA damage signalling pathways, including a significant down-regulation in transcription of the genes ATR, BRCA1 and MAPK12. Increases in the transcription of XRCC3 and GADD45· genes are also reported. Regulation of these genes could potentially have profound effects on colorectal cancer cells and may play a role in the observed chemoprotective effect of aspirin in vivo. Although a correlation was not seen between transcript and protein levels of ATR, BRCA1 and GADD45·, an increase in XRCC3 encoded protein expression upon aspirin treatment in SW480 cells was observed by immunoblotting, immunofluorescence and immunohistochemical analysis. This is the first report of XRCC3 gene transcription and encoded protein expression being susceptible to exposure to the non-steroidal anti-inflammatory drug, aspirin. Furthermore, this study indicates that alterations in gene transcription seen in microarray studies must be verified at the protein level.

show abstract

“…21,36 Valdecoxib (a specific COX2 inhibitor) 21 attenuates the effects of statins. Aspirin 38,39 and sulindac (a nonspecific cyclooxygenase inhibitor) decreases cPLA 2 mRNA expression. 39 As cPLA 2 is the major enzyme that supplies arachidonic acid to the COX2 for the production of protective prostaglandins, augmentation of cPLA 2 activity may contributes to the protective effect of ticagrelor.…”

mentioning

confidence: 99%

Chronic Treatment With Ticagrelor Limits Myocardial Infarct Size

Nanhwan

Ling

Kodakandla

et al. 2014

ATVB

130

107

View full text Add to dashboard Cite

Objective-In a phase III clinical trial (PLATelet inhibition and patient Outcomes, PLATO), ticagrelor provided better clinical outcomes than clopidogrel in patients with acute coronary syndromes. In addition to P2Y 12 -receptor antagonism, ticagrelor prevents cell uptake of adenosine and has proven able to augment adenosine effects. Adenosine protects the heart against ischemia-reperfusion injury. We compared the effects of clopidogrel and ticagrelor on myocardial infarct size (IS). Approach and Results-Rats received oral ticagrelor (0, 75, 150, or 300 mg/kg/d) or clopidogrel (30 or 90 mg/kg/d) for 7 days and underwent 30-minute coronary artery ligation and 24-hour reperfusion. Area at risk was assessed by blue dye and IS by 2,3,5-triphenyl-tetrazolium-chloride. Cyclooxygenase-2 (COX2) enzyme activity was assessed by ELISA and expression by real-time polymerase chain reaction. Mechanism responsible was explored using adenosine-receptor antagonist (CGS15943, an A 2A /A 1 antagonist) or cyclooxygenase inhibition by either aspirin (5, 10, or 25 mg/kg) or specific cyclooxygenase-1 (SC560) or COX2 (SC5815) inhibitors. Ticagrelor, dose-dependently, reduced IS, whereas clopidogrel had no effect. Adenosine-receptor antagonism blocked the ticagrelor effect and COX2 inhibition by SC5815, or high-dose aspirin attenuated the IS-limiting effect of ticagrelor, whereas cyclooxygenase-1 inhibition or low-dose aspirin had no effect. Ticagrelor, but not clopidogrel, upregulated COX2 expression and activity. Also this effect was blocked by adenosine-receptor antagonism. Ticagrelor, but not clopidogrel, increased Akt and endothelial nitric oxide synthase phosphorylation. Conclusions-Ticagrelor Nanhwan et al Ticagrelor Limits Infarct Size 2079and that higher doses of aspirin may attenuate COX2 activity 1 and thereby part of the beneficial effects mediated by ticagrelor.In this study, we evaluated whether pretreatment with ticagrelor or clopidogrel limits myocardial IS, using an experimental model of transient mechanical coronary artery occlusion that is independent of intraluminal thrombus formation. Next, we studied the signaling pathways mediating this protective effect with special emphasis on the role of adenosine-receptor activation and COX2 activity. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Ticagrelor Limits Myocardial ISA total of 8 rats died during surgery (2 in the control, 1 in the ticagrelor 75 mg/kg/d, 1 in the ticagrelor 150 mg/kg/d, 2 in the clopidogrel 30 mg/kg/d, and 2 in the clopidogrel 90 mg/kg/d group). Body weight, left ventricular (LV) weight, and the size of the area at risk (AR) were comparable among groups (Table 1). IS, expressed as percentage of the LV (Table 1) or percentage of the AR ( Figure 1A), was significantly and dose-dependently reduced in the ticagrelor-treated animals, whereas clopidogrel at 30 and 90 mg/kg/d had no effect. Hemodynamic data are presented in Figure IA and IB in the online-only Data Supplement.Plasma levels of ticagrelor 16 ho...

show abstract

Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells

Cited by 15 publications

References 29 publications

Anti-proliferative Effects of β-ionone on Human Lung Cancer A-549 Cells

Anti-proliferative Effects of β-ionone on Human Lung Cancer A-549 Cells

Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line

Chronic Treatment With Ticagrelor Limits Myocardial Infarct Size

Contact Info

Product

Resources

About