Induction of cell growth arrest and apoptotic cell death in human breast cancer MCF-7 cells by the COX-1 inhibitor FR122047

Jeong, Hakyung; Kim, Jung-Hyun; Choi, Hye Yeon; Lee, Eung-Ryoung; Cho, Ssang-Goo

doi:10.3892/or_00000866

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…Up-regulation of COX-1 gene expression in tumor tissues compared to normal tissue has been demonstrated also by whole genome expression analysis of breast carcinomas [79]. Moreover, induction of cell growth arrest and apoptosis are induced in MCF-7 human breast cell line in vitro by the COX-1 inhibitor FR122047 [80], and additive effects on tumor cell growth by COX-1 and COX-2 inhibitors are induced in vitro [81] and in vivo [82].…”

Section: Cox-1 Involvement In Neoplastic Diseasesmentioning

confidence: 99%

“…The COX-1-selective inhibitor, 4,5-bis(4-methoxyphenyl)-2-[(1-methylpiperazin-4-yl)carbonyl]thiazole (FR122047) was originally developed as antiplatelet agent devoid of ulcerogenic effects [173], and investigated as analgesic agent [174], or used as tool for studying the involvement of COX-1 as well as the role of prostanoids generated along the COX-1 and COX-2 pathways in various models of inflammation [175,176]. The antitumor activity of FR122047 has been investigated in vitro on MCF-7 breast cancer cells [80]. FR122047 treatment inhibits in vitro cell growth of MCF-7 cells, and induces apoptotic cell death that is mechanistically independent from treatment-associated ROS production, as well as from PGE 2 production inhibition.…”

Section: Antitumor Activity Of Cox-1 Selective Inhibitorsmentioning

confidence: 99%

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Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature

2018

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Prostaglandins and thromboxane are lipid signaling molecules deriving from arachidonic acid by the action of the cyclooxygenase isoenzymes COX-1 and COX-2. The role of cyclooxygenases (particularly COX-2) and prostaglandins (particularly PGE2) in cancer-related inflammation has been extensively investigated. In contrast, COX-1 has received less attention, although its expression increases in several human cancers and a pathogenetic role emerges from experimental models. COX-1 and COX-2 isoforms seem to operate in a coordinate manner in cancer pathophysiology, especially in the tumorigenesis process. However, in some cases, exemplified by the serous ovarian carcinoma, COX-1 plays a pivotal role, suggesting that other histopathological and molecular subtypes of cancer disease could share this feature. Importantly, the analysis of functional implications of COX-1-signaling, as well as of pharmacological action of COX-1-selective inhibitors, should not be restricted to the COX pathway and to the effects of prostaglandins already known for their ability of affecting the tumor phenotype. A knowledge-based choice of the most appropriate tumor cell models, and a major effort in investigating the COX-1 issue in the more general context of arachidonic acid metabolic network by using the systems biology approaches, should be strongly encouraged.

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Section: Cox-1 Involvement In Neoplastic Diseasesmentioning

confidence: 99%

Section: Antitumor Activity Of Cox-1 Selective Inhibitorsmentioning

confidence: 99%

Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature

2018

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“…Interestingly, there is evidence that COX-1 plays a pivotal role in some tumors, and COX-1 and COX-2 operate in a coordinative manner [ 5 ]. The ability of COX-1 inhibitors to arrest cell growth and cause poptosis has already been demonstrated [ 6 ]. Furthermore, simultaneous drug-induced reduction of the COX-1 and COX-2 activity has superior effects on the growth of tumor cells in vitro [ 7 ] and in vivo [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Zeise’s Salt Derivatives Bearing Substituted Acetylsalicylic Acid Substructures as Cytotoxic COX Inhibitors

Weninger,

Sagasser,

Obermoser

et al. 2023

Pharmaceutics

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Zeise’s salt derivatives of the potassium trichlorido[η2-((prop-2-en/but-3-en)-1-yl)-2-acetoxybenzoate]platinate(II) type (ASA-Prop-PtCl3/ASA-But-PtCl3 derivatives) were synthesized and characterized regarding their structure, stability, and biological activity. It is proposed that the leads ASA-Prop-PtCl3 and ASA-But-PtCl3 interfere with the arachidonic acid cascade as part of their mode of action to reduce the growth of COX-1/2-expressing tumor cells. With the aim to increase the antiproliferative activity by strengthening the inhibitory potency against COX-2, F, Cl, or CH3 substituents were introduced into the acetylsalicylic acid (ASA) moiety. Each structural modification improved COX-2 inhibition. Especially compounds with F substituents at ASA-But-PtCl3 reached the maximum achievable inhibition of about 70% already at 1 µM. The PGE2 formation in COX-1/2-positive HT-29 cells was suppressed by all F/Cl/CH3 derivatives, indicating COX inhibitory potency in cellular systems. The CH3-bearing complexes showed the highest cytotoxicity in COX-1/2-positive HT-29 cells with IC50 values of 16–27 µM. In COX-negative MCF-7 cells, they were 2–3-fold less active. These data clearly demonstrate that it is possible to increase the cytotoxicity of ASA-Prop-PtCl3 and ASA-But-PtCl3 derivatives by enhancing COX-2 inhibition.

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Cytoplasmic PPARγ is a marker of poor prognosis in patients with Cox-1 negative primary breast cancers

Shao¹,

Kühn²,

Mayr

et al. 2020

J Transl Med

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Background: The aim of this study was to investigate the expression of the nuclear receptor PPARγ, together with that of the cyclooxygenases Cox-1 and Cox-2, in breast cancer (BC) tissues and to correlate the data with several clinicobiological parameters including patient survival. Methods: In a well characterized cohort of 308 primary BC, PPARγ, Cox-1 and Cox-2 cytoplasmic and nuclear expression were evaluated by immunohistochemistry. Correlations with clinicopathological and aggressiveness features were analyzed, as well as survival using Kaplan-Meier analysis. Results: PPARγ was expressed in almost 58% of the samples with a predominant cytoplasmic location. Cox-1 and Cox-2 were exclusively cytoplasmic. Cytoplasmic PPARγ was inversely correlated with nuclear PPARγ and ER expression, but positively with Cox-1, Cox-2, and other high-risk markers of BC, e.g. HER2, CD133, and N-cadherin. Overall survival analysis demonstrated that cytoplasmic PPARγ had a strong correlation with poor survival in the whole cohort, and even stronger in the subgroup of patients with no Cox-1 expression where cytoplasmic PPARγ expression appeared as an independent marker of poor prognosis. In support of this cross-talk between PPARγ and Cox-1, we found that Cox-1 became a marker of good prognosis only when cytoplasmic PPARγ was expressed at high levels. Conclusion: Altogether, these data suggest that the relative expression of cytoplasmic PPARγ and Cox-1 may play an important role in oncogenesis and could be defined as a potential prognosis marker to identify specific high risk BC subgroups.

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Induction of cell growth arrest and apoptotic cell death in human breast cancer MCF-7 cells by the COX-1 inhibitor FR122047

Cited by 4 publications

References 23 publications

Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature

Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature

Development of Zeise’s Salt Derivatives Bearing Substituted Acetylsalicylic Acid Substructures as Cytotoxic COX Inhibitors

Cytoplasmic PPARγ is a marker of poor prognosis in patients with Cox-1 negative primary breast cancers

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