Sub‐millimolar concentration of the novel phenol‐based compound, 2‐hydroxy benzoate zinc, induces apoptosis in human HT‐1080 fibrosarcoma cells

Mahdi, Jassem G.; Pepper, Chris; Alkarrawi, M. A.; Mahdi, Ali Jassem; Bowen, I. D.

doi:10.1111/j.1365-2184.2009.00658.x

Cited by 8 publications

(15 citation statements)

References 27 publications

(29 reference statements)

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“…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%

“…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: Cell Proliferation Vs Apoptosis and Simple Phenolic Compoundsmentioning

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%

See 1 more Smart Citation

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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“…Metal ions including calcium (Ca ) showed improved efficacy to various organic compounds against cancer cells. For example, the incorporation of Zn 2+ or Ca 2+ ions improved the apoptotic potentials of HBA compounds [4,10,16] . In addition, platinum-based anticancer drugs have proven to exert highly effective therapeutic potentials in various cancer types [17] .…”

Section: Discussionmentioning

confidence: 99%

“…Although ASA and 2-HBA exert some side effects, their derivatives exhibit less acidity and possess more apoptotic potential. For example, earlier work has highlighted the potential for 4-HBZn to induce apoptosis, particularly in primary CLL and other cancer cells [4,16] . HBCa compounds have also shown their apoptotic potential in human fibrosarcoma HT-1080 cells [10] .…”

Section: Discussionmentioning

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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Protective role of curcumin in ameliorating AFB1-induced apoptosis via mitochondrial pathway in liver cells

et al. 2018

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It is well documented that liver is the primary target organ of aflatoxin B (AFB) and curcumin proved to be effective against AFB-induced liver injury. In the present study, we investigated the preventive effects of curcumin against AFB-induced apoptosis through the molecular regulation of p53, caspase-3, Bax, caspase-9, Bcl-2 and cytochrome-C associated with mitochondrial pathway. Liver antioxidant levels were measured. The hallmarks of apoptosis were analysed by methyl green-pyronin-Y staining, transmission electron microscopy, RT-PCR and western blot. Results revealed that dietary curcumin ameliorated AFB-induced oxidative stress in a dose-dependent manner. Methyl green-pyronin-Y staining and transmission electron microscopy showed that AFB induced apoptosis and caused abnormal changes in liver cells morphology such as condensation of chromatin material, reduces cell volume and damaged mitochondria. Moreover, mRNA and protein expression results manifested that apoptosis associated genes showed up-regulation in AFB fed group. However, the supplementation of dietary curcumin (dose-dependently) alleviated the increased expression of the apoptosis associated genes at mRNA and protein level, and restored the hepatocytes normal morphology. The study provides an insight and a better understanding of the preventive mechanism of curcumin against AFB-induced apoptosis in hepatocytes and provide scientific basis for the therapeutic uses of curcumin.

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Sub‐millimolar concentration of the novel phenol‐based compound, 2‐hydroxy benzoate zinc, induces apoptosis in human HT‐1080 fibrosarcoma cells

Abstract: These results demonstrate that the novel phenolic compound 2HBZ is a potent apoptosis-inducing agent in HT-1080 cells and warrants further investigation as a potential chemotherapeutic agent in primary cancer cell models.

Cited by 8 publications

References 27 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

Protective role of curcumin in ameliorating AFB1-induced apoptosis via mitochondrial pathway in liver cells

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