The aspirin metabolite, salicylate, inhibits 7,12-dimethylbenz[a]anthracene-DNA adduct formation in breast cancer cells

Abbadessa, Giuliana; Spaccamiglio, Angela; Sartori, Matteo; Nebbia, Carlo; Dacasto, Mauro; Carlo, Francesco Di; Racca, Silvia

doi:10.3892/ijo.28.5.1131

Cited by 14 publications

(12 citation statements)

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“…Inhibiting these enzymes may impact breast carcinogenesis via multiple pathways including interference with DNA adduct formation (Abbadessa et al, 2006), angiogenesis (Masferrer et al, 2000) and aromatase production (Diaz-Cruz et al, 2005) and via increasing apoptosis (Leahy et al, 2002). Some previous studies have demonstrated that aspirin, irreversible COX-1 and COX-2 inhibitor,can induce cell apoptosis through COX-dependent and COX-independent pathways.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

Hu¹,

Du²,

Zhang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the G 0 /G 1 phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. Conclusion: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormonedependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.

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Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

Hu¹,

Du²,

Zhang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…This molecule exerts a -interaction with Phe224, which has been reported by other groups in previous in silico studies with resveratrol analogs. Figure 5 shows the binding modes calculated for all the test compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12); in this regard, it is interesting to note that compounds 3, 4, 5 and 6 exert a similar binding profile ( Figure 5A) to that observed for the reference stilbene TMS, which may account for their in vitro inhibitory activity. On the other hand, compound 7 showed a slight shift within the active 0 ,5-trimethoxystilbene (TMS) at 5 mM for 6 h. First-strand cDNA was synthesized from total RNA (1.5 mg) extracted from HepG2 cells.…”

Section: Molecular Modelingmentioning

confidence: 79%

“…On one hand, it is clear that resveratrol (3,4 0 ,5-trihydroxystilbene, Figure 1) is a naturally occurring polyphenol capable of exerting significant in vitro inhibition of the CYP1A1 enzyme 9,10 , but the data on aspirin (and salicylates in general) is still controversial. For example, salicylic acid only shows CYP1A1 inhibition at relatively high concentrations (!2.5 mM) when tested in MCF-7 cells 11 , while other reports have shown that neither aspirin nor salicylic acid significantly inhibited CYP1A1 activity 12 .…”

Section: Introductionmentioning

confidence: 90%

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Design and synthesis of resveratrol–salicylate hybrid derivatives as CYP1A1 inhibitors

Aldawsari

Elshenawy

Gendy

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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Resveratrol and aspirin are known to exert potential chemopreventive effects through modulation of numerous targets. Considering that the CYP450 system is responsible for the activation of environmental procarcinogens, the aim of this study was to design a new class of hybrid resveratrol-aspirin derivatives possessing the stilbene and the salicylate scaffolds. Using HepG2 cells, we evaluated (a) the inhibition of TCDD-mediated induction of CYP1A1 exerted by resveratrol-aspirin derivatives using the EROD assay, and (b) CYP1A1 mRNA in vitro. We observed significant inhibition (84%) of CYP1A1 activity and a substantial decrease in CYP1A1 mRNA with compound 3, compared to control. Resveratrol did not exert inhibition under the same experimental conditions. This inhibitory profile was supported by docking studies using the crystal structure of human CYP1A1. The potential effect exerted by compound 3 (the most active), provide preliminary evidence supporting the design of hybrid molecules combining the chemical features of resveratrol and aspirin.

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“…Blocking COX-1 and COX-2 may inhibit breast carcinogenesis via interfering with DNA adduct formation, inhibiting angiogenesis and aromatase expression, and via increased apoptosis [6,7,8,9]. Other important ASA-based inhibitory mechanisms of carcinogenesis are the up-regulation of tumor suppressor genes such as those coding for TP53 and Bax and the down-regulation of antiapoptotic genes such as the Bcl2 gene [10].…”

Section: Introductionmentioning

confidence: 99%

Impact of Acetylsalicylic Acid on the Clinicopathological Characteristics and Prognosis of Patients with Invasive Breast Cancer

et al. 2014

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Background: The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer. Patients and Methods: Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890). Results: The median age was 56 (range 34-82) years in both groups. ASA users had a significantly lower incidence of grade II-III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50). Conclusion: Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients.

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The aspirin metabolite, salicylate, inhibits 7,12-dimethylbenz[a]anthracene-DNA adduct formation in breast cancer cells

Cited by 14 publications

References 0 publications

Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

Design and synthesis of resveratrol–salicylate hybrid derivatives as CYP1A1 inhibitors

Impact of Acetylsalicylic Acid on the Clinicopathological Characteristics and Prognosis of Patients with Invasive Breast Cancer

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