Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

Martı́n-Sanz, Paloma; Casado, Marta

doi:10.3748/wjg.v23.i20.3572

Cited by 33 publications

(25 citation statements)

References 60 publications

(67 reference statements)

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“…Unfortunately, the use of COX-2 inhibitors to prevent cancer is limited by the dangerous cardiovascular side effects that are associated with long-term use [129]. PGE 2 is also implicated in the promotion of many other types of cancer, including cancer of the breast [130], liver [131], lung [132], brain [133] and pancreas [134,135]. This suggests that the Cells 2020, 9, 1018 7 of 28 phenomenon by which inflammation fuels early tumour promotion may be a common feature of cancer development.…”

Section: Evidence Of Tumour-promoting Inflammation In Early Tumourigementioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

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The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

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Section: Evidence Of Tumour-promoting Inflammation In Early Tumourigementioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

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“…Among various NF-κB target genes, COX-2 is the best known for the promotion and development of inflammatory conditions including HCC and hepatic fibrosis [38]. COX-2 is an inflammatory molecule, which is induced by various stimulus including cellular stress, inflammatory, and carcinogens, subsequently releasing prostaglandin (PG) promoting tumor development and metastasis [39].…”

Section: Discussionmentioning

confidence: 99%

“…COX-2 is an inflammatory molecule, which is induced by various stimulus including cellular stress, inflammatory, and carcinogens, subsequently releasing prostaglandin (PG) promoting tumor development and metastasis [39]. The liver function has been improved by inhibiting NF-κB induced-activation of proinflammatory factors such as tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), and PGE2, and iNOS, COX-2, and matrix metallopeptidase-9 in LPSstimulated RAW 264.7 macrophages as well as in acute liver fibrosis mouse model [38,40,41]. Lignan can inhibit binding affinity between NF-κB and AP-1 transcription factors to interleukins (IL-6 promoter and IL-6) production through p38/NF-κB and AP-1 signaling pathways in cancer [42].…”

Section: Discussionmentioning

confidence: 99%

Lirioresinol B dimethyl ether inhibits NF-κB and COX-2 and activates IκBα expression in CCl4-induced hepatic fibrosis

Shehzad

Rehmat

Ul-Islam

et al. 2020

BMC Complement Med Ther

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Background: Inflammation is one of the key components in the initiation and progression of hepatic diseases. If not treated, inflammation may cause cell dysplasia, and ultimately cancer. In the current study, we investigated the anti-inflammatory and anti-cancer activities of plant isolated compound Lirioresinol B Dimethyl Ether (LBDE) extracted from the seeds of Magnolia fargesii CHENG (Magnoliaceae) against HepG2 cells as well as in BALB/C male mice. Methods: We assessed the antioxidant and anti-proliferative effects of plant compounds using DPPH assay and HepG2 cell lines. Carbon tetrachloride (CCl 4 ) and Diethylnitrosamine (DEN) were used to induce liver cell dysplasia followed by hepatocellular carcinoma (HCC) in BALB/C male mice for 12 weeks. We investigated the underlying mechanism by using histopathology and immunoblot experiments.Results: Intraperitoneal injection of LBDE (50 mg/kg body weight/day) inhibited CCl 4 -induced HCC. Free radical scavenging assay shows the strong anti-oxidant activity of LBDE. Western blot results show that LBDE downregulated nuclear factor kappa B (NFκB) and cyclooxygenase (COX-2) by preventing the phosphorylation of I kappa B alpha (IκBα) in CCl 4 treated group. LBDE also improved liver function by decreasing Alkaline Phosphatase (ALP), aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) levels. Histopathology results revealed that LBDE decreased granulomas and express normal morphology of hepatocytes.Conclusions: These preliminary results show that LBDE has the potential to inhibit CCl 4 -induced liver cell dysplasia and prevents cancer development by regulating NFκB/COX-2 activation.

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“…PGE2 is also implicated in the promotion of many other types of cancer, including cancer of the breast [112], liver [113], lung [114], brain [115], and pancreas [116,117]. This suggests that the phenomenon by which inflammation fuels early tumour promotion may be a common feature of cancer development.…”

Section: Evidence Of Tumour-promoting Inflammation In Early Tumourigementioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Preprint

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The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

show abstract

Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

Cited by 33 publications

References 60 publications

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Lirioresinol B dimethyl ether inhibits NF-κB and COX-2 and activates IκBα expression in CCl4-induced hepatic fibrosis

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

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