Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2

Pepper, Christopher John; Mahdi, Jassem G.; Buggins, A. G. S.; Hewamana, Saman; Walsby, Elisabeth Jane; Mahdi, Eamon J.; Al-Hazaa, Amal A.; Mahdi, Ali Jassem; Lin, T; Pearce, Laurence; Morgan, Laura; Bowen, I. D.; Brennan, Paul; Fegan, Christopher

doi:10.1111/j.1365-2184.2011.00760.x

Cited by 26 publications

(33 citation statements)

References 47 publications

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“…Another study showed that the deficiency of sharp in leads to TNF-dependent inflammation of various organs in mice while its deletion resulted in a significant reduction in the E3 ligase linear ubiquitin chain assembly complex (LUBAC) which subsequently attenuated TNF-a and CD40-mediated activation, suggesting the role of LUBAC in NF-KB activation (39). The pro-survival factor CD40 ligand (CD40L) can induce COX-2 mRNA expression essential for the synthesis of the prostaglandins (10). Thus, using anti-inflammatory drugs and/or anti-oxidants can essentially contribute to the management of inflammation homeostasis.…”

Section: Cyclooxygenase-2 Expression Proliferation and Cancer Vs Simmentioning

confidence: 99%

“…Willow bark extract, mainly contains p-D-salicin [1], and other SP complexes have been shown to down regulate cell proliferation, inhibit cell cycle, and subsequently induce apoptosis in different cell lines (8)(9)19). Other studies have shown that 2-HBA [2] or its metal ion complexes, including Na [8], Li [9], Ca [10] or Zn [11 and 12] (Fig. 4), can modulate these cellular processes and subsequently inhibit growth mostly at concentrations in the millimolar range (8)(9).…”

Section: Cell Proliferation Vs Apoptosis and Simple Phenolic Compoundsmentioning

confidence: 99%

“…Research has shown that SP compounds induce a p53 response in cancer cells resulting in cell cycle arrest and apoptosis. The treatment ofcancer cells with 2-HBNa [8], 2-HBCa [10] or 2-HBZn [11] caused the up regulation of p53, p2l, and Bax, and down regulation of the anti-apoptotic protein, Bcl-2 and arrested the cell cycle in G 1 (8)(9)(10). The mechanism of p53-dependent intrinsic apoptotic pathway activation may involve transactivation of Bax by p53 before it is translocated from the cytosol to the mitochondrial outer membrane, releasing the apoptotic factor caspases-9 from the apoptosome complex (dATP, cytochrome c, Apaf-l and pro-caspase-9) which leads to the downstream activation of caspases-3 (Fig.…”

Section: Fig 6 Proposed Intrinsic Apoptotic Pathway Induced By Salimentioning

confidence: 99%

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Pharmacological Importance of Simple Phenolic Compounds on Inflammation, Cell Proliferation and Apoptosis with a Special Reference to β-D-Salicin and Hydroxybenzoic Acid

et al. 2013

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Simple phenolic (SP) compounds are natural products that exhibit multiple pharmacological functions. The best known of these compounds is β-D-salicin, the first discovered phenolic glycoside and salicylic acid, or 2-hydroxybenzoic acid (2-HBA). Both of these compounds have attracted the interest of scientists in various interdisciplinary fields, including chemistry, pharmacology and medicine. Although β-D-salicin is found in various plants, it is often associated with willow, as it was first discovered in this species of plant. While the presence of glucose in β-D-salicin improves the physicochemical properties of the benzyl moiety, β-D-salicin itself does not have anti-inflammatory or anti-proliferative activity until it is metabolised into 2-HBA in the gastrointestinal tract and blood stream. Likewise, the majority of 2-acetoxybenzoic acid (2-ABA), or acetoxysalicylic acid also undergoes metabolic hydrolysis into 2-HBA. 2-HBA has been shown to play a role in modulating both inflammation and cancer partly through the inhibition of cyclooxygenase-2 (COX-2). It is now clear that 2-HBA most likely acts on the transcription factor NF-κB, which regulates the transcription of COX-2 thereby suppressing inflammation and cell proliferation and promoting apoptosis. Other phenolates, also exhibit anti-inflammation and anti-proliferation activities like the 4-hydroxybenzoate zinc (4-HBZn) complex, which was previously shown to preferentially inhibit COX-2 compared to 2-HBA and ASA. This review aims to collect all the available information related to β-D-salicin and other SP compounds in order to promote a new perspective of this interesting class of compounds and encourage further research into their pharmacological and clinical properties.

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Section: Cyclooxygenase-2 Expression Proliferation and Cancer Vs Simmentioning

confidence: 99%

Section: Cell Proliferation Vs Apoptosis and Simple Phenolic Compoundsmentioning

confidence: 99%

Section: Fig 6 Proposed Intrinsic Apoptotic Pathway Induced By Salimentioning

confidence: 99%

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Pharmacological Importance of Simple Phenolic Compounds on Inflammation, Cell Proliferation and Apoptosis with a Special Reference to β-D-Salicin and Hydroxybenzoic Acid

et al. 2013

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“…35 ferent cancer cells [4][5][6][7] . The assessed compounds include hydroxybenzoate (HB), 2-acetylbenzoic acid (2-ABA) or aspirin, and its precursor 2-hydroxybenzoic acid (2-HBA).…”

mentioning

confidence: 99%

“…The mechanism of these compounds is to induce apoptosis via the intrinsic pathway involving the upregulation of the expression of p53, Bax and caspase-9 [4,10,12] . In parallel, these compounds downregulated Bcl-2, an antiapoptotic protein that is able to suppress cytochrome c release and subsequently caspase-3.…”

mentioning

confidence: 99%

The effect of hydroxybenzoate calcium compounds in inducing cell death in epithelial breast cancer cells

Merghani¹,

Hazzaa²,

Mahdi³

et al. 2015

Adv Mod Oncol Res

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Hydroxybenzoate (HB) compounds have shown their significance in inducing apoptosis in primary chronic lymphocytic leukemia (CLL) and cancer cell lines, including HT-1080. The current study focuses on assessing the effects of 2-, 3-and 4-hydroxybenzoate calcium (HBCa) compounds on MCF-10A, MDA-MB231 and MCF-7 epithelial breast cell lines. The HBCa-treated cells were examined using annexin V, to measure apoptosis in the three epithelial breast cell lines, after 48 h of treatment. The results indicated that 0.5 and 2.5 mmol/L of HBCa induced cell death in a dose-dependent manner. The induction of cell death in normal MCF-10A cells was found to be significantly less (p = 0.0003-0.0068), in comparison to the malignant cell lines (MDA-MB231 and MCF-7). HBCa compounds were also found to cause cell cycle arrest in the epithelial breast cells at G1/G0. Furthermore, HBCa compounds induced the upregulation of apoptotic proteins (p53, p21, Bax and caspase-3), as well as the downregulation of the anti-apoptotic protein Bcl-2, which may suggest that apoptosis is induced via the intrinsic pathway. reast cancer is a major global health issue that mainly affects women of all age groups. It is the most common cancer worldwide, with more cases in developing countries than in developed countries [1] . Breast cancer is the second leading cause of cancer death after lung cancer in developed countries (198,000 cases, 15.4%). Incidence rates continue to increase globally except in a few high-income countries. The estimated breast cancer incidents of less developed cases in 2012 were 883,000 (52.8%) and 788,000 more developed cancer cases, with mortality rates of 324,000 (62.1%) and 198,000 (37.9%), respectively [2] . In contrast, more than 60% of breast cancer patients survive in developed countries. Lower survival rates occur in developing countries due to the lack of early detection schemes and diagnosis [3] . Statistics related to breast cancer cases have attracted the attention of various researchers to effectively treat the cancer with chemotherapy. As part of this effort, a large number of compounds have been assessed for their anticancer potential in dif-B

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Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells

et al. 2017

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Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6 signals that were differentially expressed in the stromal compartment of the follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells (AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs secreted a significantly higher level of IL-6 as compared to the counterpart AM-EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in AM-EpiCs, whereas such effects were significantly abrogated either by a specific inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling pathways, implying a role in the etiology and progression of the benign but locally invasive neoplasm. Stem Cells 2017;35:2083-2094.

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Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2

Abstract: Our results demonstrate therapeutic potential of 4HBZ and are consistent with a mechanism involving suppression of Rel A nuclear translocation and inhibition of COX-2 transcription.

Cited by 26 publications

References 47 publications

Pharmacological Importance of Simple Phenolic Compounds on Inflammation, Cell Proliferation and Apoptosis with a Special Reference to β-D-Salicin and Hydroxybenzoic Acid

Pharmacological Importance of Simple Phenolic Compounds on Inflammation, Cell Proliferation and Apoptosis with a Special Reference to β-D-Salicin and Hydroxybenzoic Acid

The effect of hydroxybenzoate calcium compounds in inducing cell death in epithelial breast cancer cells

Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells

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