Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells

Timoshenko, Alexander V.; Xu, Guoxiong; Chakrabarti, Sumontra; Lala, Peeyush K.; Chakraborty, Chandan

doi:10.1016/s0014-4827(03)00269-6

Cited by 136 publications

(138 citation statements)

References 34 publications

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“…In contrast, VEGF-A production by MDA-MB-231 cells was not reduced in the presence of these inhibitors ( Figure 4A). We had earlier shown that these concentrations of indomethacin and NS-398, respectively, suppressed PGE 2 production by 72 and 94% in MDA-MB-231 cells (Timoshenko et al, 2003). Concanavalin A (Con A), earlier shown to stimulate PGE 2 production by MDA-MB-231 cells (Timoshenko et al, 2003), also stimulated VEGF-C as well as VEGF-A production, which were significantly blocked with the COX-1/2 inhibitor ( Figure 4A).…”

Section: Resultsmentioning

confidence: 83%

“…We had earlier shown that these concentrations of indomethacin and NS-398, respectively, suppressed PGE 2 production by 72 and 94% in MDA-MB-231 cells (Timoshenko et al, 2003). Concanavalin A (Con A), earlier shown to stimulate PGE 2 production by MDA-MB-231 cells (Timoshenko et al, 2003), also stimulated VEGF-C as well as VEGF-A production, which were significantly blocked with the COX-1/2 inhibitor ( Figure 4A). This inhibition was much higher in the case of VEGF-C. A small inhibitory effect on VEGF-C but not VEGF-A was also observed with the selective COX-1 inhibitor SC-560 (5 mM) ( Figure 4A and B) but it was significantly less than that caused by the selective COX-2 inhibitor NS-398 ( Figure 4A).…”

Section: Resultsmentioning

confidence: 83%

“…All agents (pharmacological agents, inhibitors), the effects of which were tested on VEGF-C production by human breast cancer cells were also tested under identical conditions for possible effects on cell proliferation/survival using the MTT Cell Proliferation Kit I from Roche Diagnostics (Laval, QC, Canada), as reported earlier (Timoshenko et al, 2003).…”

Section: Mtt Assay For Cell Proliferation/survivalmentioning

confidence: 99%

“…For example, EP1, EP2 and EP4 contributed to colon carcinogenesis (Hull et al, 2004), and EP2 was shown to be required for COX-2-mediated mammary hyperplasia (Chang et al, 2005). Furthermore, EP4 contributed to the stimulation of migration of colorectal (Sheng et al, 2001) and breast (Timoshenko et al, 2003) cancer cells. EP4 receptors were also responsible for an upregulation of iNOS gene expression under inducible conditions in murine breast cancer cells that increased their invasive capacity (Timoshenko et al, 2004), as well as in osteoclast development and bone metastasis in a breast cancer model (Ohshiba et al, 2003).…”

mentioning

confidence: 99%

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COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

et al. 2006

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Increased expression of COX-2 or VEGF-C has been correlated with progressive disease in certain cancers. Present study utilized several human breast cancer cell lines (MCF-7, T-47D, Hs578T and MDA-MB-231, varying in COX-2 expression) as well as 10 human breast cancer specimens to examine the roles of COX-2 and prostaglandin E (EP) receptors in VEGF-C expression or secretion, and the relationship of COX-2 or VEGF-C expression to lymphangiogenesis. We found a strong correlation between COX-2 mRNA expression and VEGF-C expression or secretion levels in breast cancer cell lines and VEGF-C expression in breast cancer tissues. Expression of LYVE-1, a selective marker for lymphatic endothelium, was also positively correlated with COX-2 or VEGF-C expression in breast cancer tissues. Inhibition of VEGF-C expression and secretion in the presence of COX-1/2 or COX-2 inhibitors or following downregulation of COX-2 with COX-2 siRNA established a stimulatory role COX-2 in VEGF-C synthesis by breast cancer cells. EP1 as well as EP4 receptor antagonists inhibited VEGF-C production indicating the roles of EP1 and EP4 in VEGF-C upregulation by endogenous PGE 2 . Finally, VEGF-C secretion by MDA-MB-231 cells was inhibited in the presence of kinase inhibitors for Her-2/neu, Src and p38 MAPK, indicating a requirement of these kinases for VEGF-C synthesis. These results, for the first time, demonstrate a regulatory role of COX-2 in VEGF-C synthesis (and thereby lymphangiogenesis) in human breast cancer, which is mediated at least in part by EP1/EP4 receptors.

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Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 83%

Section: Mtt Assay For Cell Proliferation/survivalmentioning

confidence: 99%

mentioning

confidence: 99%

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COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

et al. 2006

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“…We examined the expression of the EP receptors in HCA-7 cells and MCF-7 cells using real time PCR. The MCF-7 cells were used as a positive control since these cells have been shown to express the EP1, EP2, and EP4 receptors [24]. We found that the EP1, EP2, and EP4 mRNAs were expressed in HCA-7 cells (Fig.1).…”

Section: Ep4 Receptor Mediates Pge 2 -Induced Phosphorylation Of Erksmentioning

confidence: 82%

The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

Cherukuri

Chen

Goulet

et al. 2007

Experimental Cell Research

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Accumulating evidence indicates that elevated levels of prostaglandin E 2 (PGE 2 ) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE 2 exerts its effects through four G-protein coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE 2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE 2 -induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE 2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE 2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE 2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE 2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer.

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Rationally Developed Organic Salts of Tolfenamic Acid and Its β‐Alanine Derivatives for Dual Purposes as an Anti‐Inflammatory Topical Gel and Anticancer Agent

Parveen

Sravanthi

Dastidar

2017

Chemistry An Asian Journal

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A new series of primary ammonium monocarboxylate (PAM) salts of a nonsteroidal anti-inflammatory drug (NSAID), namely, tolfenamic acid (TA), and its β-alanine derivatives were generated. Nearly 67 % of the salts in the series showed gelling abilities with various solvents, including water (biogenic solvent) and methyl salicylate (typically used for topical gel formulations). Gels were characterized by rheology, electron microscopy, and so forth. Structure-property correlations based on single-crystal and powder XRD data of several gelator and nongelator salts revealed intriguing insights. Studies (in vitro) on an aggressive human breast cancer cell line (MDA-MB-231) with the l-tyrosine methyl ester salt of TA (S7) revealed that the hydrogelator salt was more effective at killing cancer cells than the mother drug TA (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay); displayed better anti-inflammatory activity compared with that of TA (prostaglandin E assay); could be internalized within the cancer cells, as revealed by fluorescence microscopy; and inhibited effectively migration of the cancer cells. Thus, the easily accessible ambidextrous gelator salt S7 can be used for two purposes: as an anti-inflammatory topical gel and as an anticancer agent.

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Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells

Cited by 136 publications

References 34 publications

COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

Rationally Developed Organic Salts of Tolfenamic Acid and Its β‐Alanine Derivatives for Dual Purposes as an Anti‐Inflammatory Topical Gel and Anticancer Agent

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