Expression of Lipoxygenase in Human Bladder Carcinoma and Growth Inhibition by Its Inhibitors

Yoshimura, Rikio; Matsuyama, Masahide; Tsuchida, Kenji; Kawahito, Yutaka; Sano, Hajime; Nakatani, Tatsuya

doi:10.1097/01.ju.0000080296.54262.c8

Cited by 68 publications

(76 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,[9][10][11] In the current paper, we investigated the flavonoids, baicalein and apigenin, as possible 12-hLO selective inhibitors, because, baicalein has been used in numerous citations as a selective inhibitor against 12-hLO in mammalian cells. [37][38][39][40][41][42][43] In order to investigate this detergent effect further, we included another flavonoid, apigenin, which we previously demonstrated to be a potent LO inhibitor. 16 Apigenin is a good candidate for comparison with baicalein due to its similar structure to baicalein, except for the re-positioning of one alcohol group (Figure 1).…”

Section: Insert Figure 4 Discussionmentioning

confidence: 99%

“…One specific flavonoid LO inhibitor is baicalein, a major component in the root of Scutellaria baicalensis (1.9% of total root), and has been shown to induce apoptosis in breast, prostate, colon and pancreatic cancer cell lines. [33][34][35][36] In all cases, the potency of baicalein is thought to be due to the selective inhibition of platelet 12-hLO, [37][38][39][40][41][42][43] thus interrupting only part of the arachidonic acid metabolic pathway, however, the basis of this supposition is unclear. The most cited reference, by Sekiya and Okuda, indicated only that baicalein was selective to platelet 12-hLO versus cyclooxygenase (COX), but not versus the other LO isozymes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases

Deschamps

Kenyon

Holman

2006

Bioorganic & Medicinal Chemistry

143

126

View full text Add to dashboard Cite

Abstract. Lipoxygenases (LO) have been implicated in asthma, immune disorders, and various cancers and as a consequence, there is great interest in isolating selective LO isozyme inhibitors.Currently, there is much use of baicalein as a selective human platelet 12-LO (12-hLO) inhibitor however, our current steady-state inhibition data indicates that baicalein is not selective against 12-hLO versus human reticulocyte 15-LO-1 (15-hLO-1) (15/12 = 1.3), in vitro. However, in the presence of detergents baicalein is slightly more selective (15/12 = 7), which may imply greater selectivity in a cell based assay but has yet to be proven. The mechanism of baicalein inhibition of 15-hLO is reductive, which computer docking suggests is through direct binding of the catecholic moiety of baicalein to the iron. A structurally related flavonoid, apigenin, is not reductive, however, computer docking suggests a hydrogen bond with Thr591, may account for its inhibitor potency.

show abstract

Section: Insert Figure 4 Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases

Deschamps

Kenyon

Holman

2006

Bioorganic & Medicinal Chemistry

143

126

View full text Add to dashboard Cite

show abstract

“…In a more generic approach, a number of investigations have found a correlation between mRNA expression levels of 5-and/or 12-LOX and cancer pathobiology, whereby increased LOX expression levels were noted in a broad range of cancers including breast, pancreatic, prostate, lung, urinary bladder, leukaemia and colon cancer [63,64,65,66,67,68,69]. With regards to 15-LOX, there is evidence for opposing theories on correlation of expression levels with carcinogenesis where both over-and under-expression has been observed in cancerous cells [70,71].…”

Section: Figurementioning

confidence: 99%

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

Hyde

Missailidis

2009

International Immunopharmacology

142

101

View full text Add to dashboard Cite

Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention.

show abstract

“…Among these, recent studies have revealed potential roles of the 5-, 12-, and 15-lipoxygenase (LO) pathways in cancer progression. For example, 5-and 12-LO are overexpressed in bladder cancer tissues and LO inhibitors inhibited growth of bladder cancer and induced apoptosis (Yoshimura et al, 2003;Hayashi et al, 2006). In accordance with the suggested role of 12-LO in cancer, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a 12-LO pathway metabolite, was shown to influence tumor progression (Nie et al, 2006).…”

Section: Introductionmentioning

confidence: 81%

Up-regulation of BLT2 is critical for the survival of bladder cancer cells

et al. 2011

View full text Add to dashboard Cite

The incidence rates of urinary bladder cancer continue to rise yearly, and thus new therapeutic approaches and early diagnostic markers for bladder cancer are urgently needed. Thus, identifying the key mediators and molecular mechanisms responsible for the survival of bladder cancer has valuable implications for the development of therapy. In this study, the role of BLT2, a receptor for leukotriene B 4 (LTB 4 ) and 12(S)-hydroxyeicosatetraenoic acid (HETE), in the survival of bladder cancer 253J-BV cells was investigated. We found that the expression of BLT2 is highly elevated in bladder cancer cells. Also, we observed that blockade of BLT2 with an antagonist or BLT2 siRNA resulted in cell cycle arrest and apoptotic cell death, suggesting a role of BLT2 in the survival of human bladder cancer 253J-BV cells. Further experiments aimed at elucidating the mechanism by which BLT2 mediates survival revealed that enhanced level of reactive oxygen species (ROS) are generated via a BLT2-dependent up-regulation of NADPH oxidase members NOX1 and NOX4. Additionally, we observed that inhibition of ROS generation by either NOX1/4 siRNAs or treatment with an ROS-scavenging agent results in apoptotic cell death in 253J-BV bladder cancer cells. These results demonstrated that a 'BLT2-NOX1/4-ROS' cascade plays a role in the survival of this aggressive bladder cancer cells, thus pointing to BLT2 as a potential target for anti-bladder cancer therapy.

show abstract

Expression of Lipoxygenase in Human Bladder Carcinoma and Growth Inhibition by Its Inhibitors

Abstract: Lipoxygenase is induced in bladder cancer. Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. Thus, lipoxygenase may become a new target in the treatment of bladder tumors.

Cited by 68 publications

References 18 publications

Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases

Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

Up-regulation of BLT2 is critical for the survival of bladder cancer cells

Contact Info

Product

Resources

About