Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

Bernard, Matthew P.; Bancos, Simona; Sime, Patricia J.; Phipps, Richard P.

doi:10.2174/138161208785294654

Cited by 60 publications

(50 citation statements)

References 107 publications

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“…Numerous studies have demonstrated that COX molecules are involved in the onset and progression of a variety of malignancies and are overexpressed in ovarian cancer (13,23,24). Other studies have found that COX-1, but not COX-2, is the predominant COX isoform expressed in human ovarian cancer (11,12,15,25).…”

Section: Discussionmentioning

confidence: 99%

Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo

Liu

Cai

et al. 2012

Oncology Letters

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Abstract. This study was designed to investigate the effects of a cyclooxygenase (COX)-1 inhibitor, SC-560, administered in combination with taxol, on the molecular mechanisms of antitumor efficacy in a SKOV-3 human ovarian carcinoma cell xenograft-bearing mouse model. The mice were treated with 6 mg/kg/day SC-560 by gavage twice every other day and20 mg/kg taxol by intraperitoneal injection once a week for three weeks. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) mRNA levels of ovarian cancer were detected in the tumor tissues using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The index of proliferating and apoptotic cells in the tumor tissues was determined by staining for Ki-67 and using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, respectively. On day 7 after the end of administration, the tumor volume of mice in the combination group was reduced by 55.35% compared with that of the control mice, and the difference was statistically significant (P<0.05). In the combination group, the expression of VEGF, MVD and the cell proliferation index were inhibited significantly, while the apoptotic index was notably increased (all P<0.01, compared with the control group). Our results indicate that the molecular mechanisms of the antitumor efficacy of SC-560 combined with taxol therapy may act in part by inhibiting tumor angiogenesis, reducing cell proliferation and inducing cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo

Liu

Cai

et al. 2012

Oncology Letters

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“…9 An involvement of COX-2 activity and PGE 2 production in carcinogenesis has been reported in solid tissue cancers such as colonic, breast and lung carcinoma, 9 as well as some hematological malignancies. 10 Recent findings suggest a role for COX-2/PGE 2 signaling in the regulation of the tumor microenvironment. 11 The inhibition of prostaglandin synthesis by a long-term use of non-steroidal antiinflammatory drugs has been shown to have a chemopreventive effect on several cancer types.…”

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confidence: 99%

COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF)

et al. 2010

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Cancer often originates from a site of persistent inflammation, and the mechanisms turning chronic inflammation into a driving force of carcinogenesis are intensely investigated. Cyclooxygenase-2 (COX-2) is an inducible key modulator of inflammation that carries out the rate-limiting step in prostaglandin synthesis. Aberrant COX-2 expression and prostaglandin E 2 (PGE 2 ) production have been implicated in tumorigenesis. In this study we show that COX-2 is ectopically expressed in malignant T-cell lines from patients with cutaneous T-cell lymphoma (CTCL) as well as in situ in lymphocytic cells in 21 out of 22 patients suffering from mycosis fungoides (MF) in plaque or tumor stage. COX-2 is not expressed in lymphocytes of 11 patients with patch-stage MF, whereas sporadic COX-2 staining of stromal cells is observed in the majority of patients. COX-2 expression correlates with a constitutive production of PGE 2 in malignant T cells in vitro. These cells express prostaglandin receptors EP3 and EP4 and the receptor antagonist as well as small interfering RNA (siRNA) directed against COX-2, and specific COX-2 inhibitors strongly reduce their spontaneous proliferation. In conclusion, our data indicate that COX-2 mediated PGE 2 exerts an effect as a tumor growth factor in MF.

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“…Concerning hematological malignancies, Bernard et al (6) highlighted the recent interest in studying and modulating COX-2 expression in cells of hematopoietic origin. They described the different studies that were conducted on the impact of COX-2 expression in hematological diseases and showed that chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma all highly express COX-2 and that elevated COX-2 expression is often correlated with decreased survival of patients with hematological malignancies (6).…”

Section: Introductionmentioning

confidence: 99%

“…They described the different studies that were conducted on the impact of COX-2 expression in hematological diseases and showed that chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma all highly express COX-2 and that elevated COX-2 expression is often correlated with decreased survival of patients with hematological malignancies (6). As for acute myeloid leukemia, COX-2 has been shown to be expressed in various cell lines and functional genetic variations of COX-2 have been recently correlated to susceptibility to acute myeloid leukemia (7,8).…”

Section: Introductionmentioning

confidence: 99%

“…The interest on COX-2 activity in hematological malignancies has also been reinforced by the use of NSAIDs and COX-2 selective inhibitors in vitro, to induce proliferation arrest and apoptosis in leukemia cells (6,10,11). Furthermore, it was also shown that targeting COX-2 reduced toxicity toward low-dose chemotherapy with vinblastine and extended survival in an erythroleukemia model of juvenile mice with Friend disease (12).…”

Section: Introductionmentioning

confidence: 99%

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Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Diab

Fidanzi

Léger

et al. 2015

International Journal of Oncology

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Abstract. The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX-2 (HEL cell line) or not (K562 cell line). Moreover, we made use of COX-2 cDNA to overexpress COX-2 in K562 cells. In light of the reported chemopreventive and chemosensitive effects of natural products on various tumor cells and animal models, we postulated that our Bl extract may mediate their effects through apoptosis induction with suppression of cell survival pathways. Our study is the first report on the specific examination of intrinsic apoptosis and Akt/NF-κB/COX-2 pathways in human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl extract treatment on K562 cells was observed resulting in activation of the late markers of apoptosis with caspase-3 activation, PARP cleavage and DNA fragmentation. Whereas, we showed that Bl extract reduced significantly expression of COX-2 by a dose-dependent manner in HEL and K562 (COX-2 + ) cells. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of Bl extract in human erythroleukemia cells. We observed that the Bl extract is clearly more active than the berberine alone on the induction of DNA fragmentation in human erythroleukemia cells.

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Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

Cited by 60 publications

References 107 publications

Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo

Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo

COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF)

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

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