Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines

Seo, Kyoung Won; Coh, Ye Rin; Rebhun, Robert B.; Ahn, Jin Ok; Han, Sei Myung; Lee, Hee Woo; Youn, Hwa Young

doi:10.1016/j.rvsc.2014.03.003

Cited by 22 publications

(21 citation statements)

References 27 publications

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“…It has been reported that COX-2 pathway is closely associated with tumor cell growth and is a crucial molecule in the development of malignant tumors, and angiogenesis (15,16), anti-apoptosis (17), invasiveness (18) and proliferation (19). In the present study, we found that NS-398 (an inhibitor of COX-2) increased caspase-3 expression, which is consistent with previous research results (17,31). In addition, treatment of cells with 400 µmol/l NaHS for 24 h promoted the expression level of COX-2, along with the NaHS-induced pro-proliferative effect and anti-apoptosis.…”

Section: Discussionsupporting

confidence: 93%

“…Previous studies have demonstrated that MAPKs (p38 MAPK and ERK1/2) also activate other signaling cascades, such as cyclooxygenase-2 (COX-2) (13,14), in a variety of cancer cell types. COX-2 expression is closely associated with tumor cell growth and is a crucial molecule in the development of malignant tumors, and angiogenesis (15,16), anti-apoptosis (17), invasiveness (18) and proliferation (19). In addition, a previous study demonstrated that COX-2 was activated dependent on the ERK1/2 pathway in glioma (20).…”

Section: Introductionmentioning

confidence: 99%

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Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

et al. 2015

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Abstract. Hydrogen sulfide (H 2 S) participates in multifarious physiological and pathophysiologic progresses of cancer both in vitro and in vivo.We have previously demonstrated that exogenous H 2 S promoted liver cancer cells proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway. However, the effects of H 2 S on cancer cell proliferation and apoptosis are controversial and remain unclear in C6 glioma cells. The present study investigated the effects of exogenous H 2 S on cancer cells growth via activating p38 MAPK/ERK1/2-COX-2 pathways in C6 glioma cells. C6 glioma cells were treated with 400 µmol/l NaHS (a donor of H 2 S) for 24 h. The expression levels of phosphorylated (p)-p38 MAPK, total (t)-p38 MAPK, p-ERK1/2, t-ERK1/2, cyclooxygenase-2 (COX-2) and caspase-3 were measured by western blotting assay. Cell viability was detected by Cell Counting . Apoptotic cells were observed by Hoechst 33258 staining assay. Cell proliferation was directly detected under fully automatic inverted microscope. Exposure of C6 glioma cells to NaHS resulted in cell proliferation, as evidenced by an increase in cell viability. In addition, NaHS treatment reduced apoptosis, as indicated by the decreased apoptotic percentage and the cleaved caspase-3 expression. Importantly, exposure of the cells to NaHS increased the expression levels of p-p38 MAPK, p-ERK1/2 and COX-2. Notably, co-treatment of C6 glioma cells with 400 µmol/l NaHS and AOAA (an inhibitor of CBS) largely suppressed the above NaHS-induced effects. Combined treatment with NaHS and SB203580 (an inhibitor of p38 MAPK) or PD-98059 (an inhibitor of ERK1/2) resulted in the synergistic reduction of COX-2 expression and increase of caspase-3 expression, a decreased number of apoptotic cells, along with decreased cell viability. Combined treatment with NS-398 (an inhibitor of COX-2) and NaHS also resulted in the synergistic increase of caspase-3, a decreased in the number of apoptotic cells and the decrease in cell viability. The findings of the present study provide novel evidence that p38 MAPK/ERK1/2-COX-2 pathways are involved in NaHS-induced cancer cell proliferation and anti-apoptosis in C6 glioma cells.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

et al. 2015

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“…recently, Seo et al reported that celecoxib exerted antitumor effects in both coX-2-expressing and -non-expressing canine melanoma cells (56). consistent with this, the current study demonstrated that a high dose of celecoxib induced growth arrest and apoptosis in canine mammary tumor cells, regardless of coX-2 expression.…”

Section: Discussionsupporting

confidence: 90%

Celecoxib exerts antitumor effects in canine mammary tumor cells via COX-2-independent mechanisms

Tamura

Saito

Murata

et al. 2015

International Journal of Oncology

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Abstract. celecoxib plays antitumor roles via multiple mechanisms in a variety of human cancers. the aim of this study was to clarify the mechanism of action of celecoxib in canine mammary tumors. We examined the antitumor effects of celecoxib in aZacB canine mammary tumor cells expressing low levels of cyclooxygenase-2 (coX-2) to minimize the effect of coX-2 on its activity. our data revealed that celecoxib inhibited cell proliferation mainly via COX-2-independent mechanisms. Specifically, celecoxib decreased the proportion of cells in S phase and increased g2/M arrest, which was associated with increased expression of the cyclin-dependent kinase inhibitors (cDKis) p21 and p27. in addition, treatment with celecoxib downregulated coX-2 expression, and induced apoptosis via both the intrinsic and extrinsic pathways. These findings suggest that celecoxib might be a useful agent for the treatment of canine mammary tumors, regardless of coX-2 expression. in the future, it might be possible to use a combination of celecoxib and other antitumor agents to treat canine mammary tumors.

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“…To improve the outcome of both canine and human melanoma patients, biomarkers that could be used as therapeutic targets are sought. COX-2 is a potential target for chemoprevention and therapy in several cancer types [19][20][21][22] and, as suggested previously, canine melanoma patients might benefit from the use of specific COX-2 inhibitors [12,14,22].…”

Section: Introductionmentioning

confidence: 99%

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

et al. 2016

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Cyclooxygenase-2 (COX-2) is known to be involved in tumour progression and has been suggested as a therapeutic target in many human and animal malignancies. A number of different pathways subjacent to cancer hallmarks are considered to be involved in COX-2-mediated tumour progression, although these are still largely undefined. Our aim is to investigate associations between COX-2 expression and angiogenesis, proliferation and the inflammatory microenvironment in canine melanocytic tumours. Understanding the involvement of COX-2 with cancer hallmarks might enable us to adapt therapeutic strategies for canine melanomas, an aggressive and often lethal malignancy with value in comparative oncology. Immunohistochemical staining of COX-2, Ki-67 (proliferation index), vascular endothelial growth factor (VEGF), factor VIII (microvessel density), CD3 (lymphocytes) and MAC387 (macrophages) was performed in 51 melanocytic tumours (31 malignant melanomas, 20 melanocytomas). Statistical associations between COX-2 and the other parameters detected were analysed. In melanocytic tumours (n=51), both COX-2 labelling extension and intensity showed a statistically significant association with angiogenesis by factor VIII, VEGF, Ki-67, CD3+ T lymphocytes and MAC387. Within malignant melanomas, COX-2 expression has shown significant associations with microvessel density (factor VIII), lymphocyte and macrophage infiltration and, considering all melanocytic tumours, COX-2 was also associated with VEGF intensity and Ki-67 cell proliferation. Our results point to a role for COX-2 in angiogenesis and in the establishment of an inflammatory microenvironment, favourable to melanoma tumour progression. Further mechanistic studies are warranted to dissect molecular pathways in which COX-2 is involved. Present evidence suggests that COX-2 inhibitors might be useful as an adjuvant treatment to hinder canine melanoma progression.

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Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines

Cited by 22 publications

References 27 publications

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways

Celecoxib exerts antitumor effects in canine mammary tumor cells via COX-2-independent mechanisms

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

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