Inhibition of cyclooxygenase-1 lowers proliferation and induces macroautophagy in colon cancer cells

Wu, William; Sung, Joseph J.Y.; Wu, Yuzhong; Li, Hai To; Yu, Li; Li, Zhi Jie; Cho, Chi Hin

doi:10.1016/j.bbrc.2009.02.140

Cited by 13 publications

(12 citation statements)

References 21 publications

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“…These observations were confirmed in a further study of selective COX-1 inhibition in colon carcinogenesis [111]. A recent study demonstrated reduced proliferation and increased macroautophagy in colon cancer cells following COX-1 inhibtion [112].…”

Section: Accepted Manuscriptsupporting

confidence: 70%

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention

Cathcart¹,

O’Byrne²,

Reynolds³

et al. 2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies.COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers was significantly reduced by daily aspirin intake. A number of randomised controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors.However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk.More recently, downstream effectors of COX-signalling have been investigated in cancer development/progression. PGE 2 , which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. caners has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2 . Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed.Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field.

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Section: Accepted Manuscriptsupporting

confidence: 70%

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention

Cathcart¹,

O’Byrne²,

Reynolds³

et al. 2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…Recent findings on the relationship of COX-1 in the development of several cancers have suggested that the carcinogenic actions of COX-2 should be distinguished from those of COX-1 in the application of prostaglandin-blocking therapy for cancer treatment. Furthermore, production of prostaglandins in promoting the viability of cancer cells has been observed to result entirely from COX-1, not COX-2, in some cancer models [17,18]. The expression of COX-1 and COX-2 varied in the HNSCC cell lines used in this study.…”

Section: Discussionmentioning

confidence: 92%

The influence of cyclooxygenase-1 expression on the efficacy of cyclooxygenase-2 inhibition in head and neck squamous cell carcinoma cell lines

Park¹,

Kim²,

Choi³

et al. 2011

Anti-Cancer Drugs

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We have previously observed that cyclooxygenase-2 (COX-2) inhibition blocked the production of vascular endothelial growth factor (VEGF) in some head and neck squamous cell carcinoma (HNSCC) cells. However, as some HNSCC cells showed little response to COX-2 inhibition, although they highly expressed COX-2 and prostaglandin E2, we set out to elucidate what made this difference between them and focused on the possibility of the differential expression of COX-1. In western blotting, we found that COX-1 was expressed in SNU-1041 and SNU-1066, but not in SNU-1076 and PCI-50. Only in those cell lines without expression of COX-1 was VEGF production blocked meaningfully by small interfering RNA of COX-2. However, by cotreating with small interfering RNAs of COX-2 and COX-1, VEGF synthesis and prostaglandin E2 were inhibited in SNU-1041 and SNU-1066, similarly in SNU-1076 and PCI-50 with high expression of only COX-2. We also found that there was no difference in the pattern of prostaglandin synthesis between COX-2 and COX-1 through enzyme-linked immunosorbent assay for various prostaglandins. Our study suggests that, as COX-1 and COX-2 express and affect VEGF synthesis in HNSCC cells, we should check COX-1 expression in investigations on cancer treatment by inhibiting COX-2-induced prostaglandins.

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“…COX-2 has been intensively investigated as an essential factor involved in the development of various types of cancer; however, COX-1 has emerged as exhibiting an important function in tumor progression, particularly in colon carcinogenesis. Wu et al (17) indicted that treatment of colon cancer cells with a COX-1 inhibitor decreased cell proliferation, and induced alterations in morphological and biochemical characteristics associated with cell cycle arrest and macroautophagy. Li et al (10) identified that COX-1 is required for the maintenance of malignant characteristics of colon cancer cells or tumor promoter-induced transformation of pre-neoplastic cells, and the specific COX-1 inhibitor as a potential preventive agent against CRC.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of cyclooxygenase‑1 stimulates mitochondrial apoptosis through the NF‑κB signaling pathway in colorectal cancer cells

Ding

Lan

et al. 2018

Oncol Rep

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The prognosis of patients with colorectal cancer (CRC) remains poor owing to diagnosis typically occurring at advanced stages of the disease. The understanding of the molecular regulatory signatures of CRC may lead to the identification of biomarkers for the early detection, prevention and clinical intervention of CRC. Epidemiological studies have indicated that cyclooxygenase-1 (COX-1) serves an active function in colon carcinogenesis. However, the molecular mechanism underlying COX-1 regulation in CRC remains unknown. In the present study, COX-1 was identified to be markedly upregulated in colorectal tissues of patients with CRC, and in the CRC cell lines HCT116 and HT29. To determine the function of COX-1 in cancer development, short hairpin RNA knockdown of COX-1 was employed in HCT116 and HT29 CRC cells in the present study. The results demonstrated that silencing of COX-1 depolarized the mitochondrial membrane potential, inhibited adenosine triphosphate production, induced the generation of intracellular reactive oxygen species and triggered caspase-dependent mitochondrial apoptosis. Furthermore, depletion of COX-1 suppressed anti-apoptotic B-cell lymphoma 2 and enhanced pro-apoptotic Bcl-2-associated X protein expression by inhibiting the p65 subunit phosphorylation of nuclear factor κB (NF-κB). Taken together, the results of the present study indicated that COX-1 inhibition significantly triggered cell death by destroying the mitochondrial function that is associated with deactivation of the NF-κB signaling pathway. These results suggest COX-1 as a potential anticancer target in CRC.

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Inhibition of cyclooxygenase-1 lowers proliferation and induces macroautophagy in colon cancer cells

Cited by 13 publications

References 21 publications

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention

The influence of cyclooxygenase-1 expression on the efficacy of cyclooxygenase-2 inhibition in head and neck squamous cell carcinoma cell lines

Downregulation of cyclooxygenase‑1 stimulates mitochondrial apoptosis through the NF‑κB signaling pathway in colorectal cancer cells

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