Acetylsalicylic acid exhibits anticlastogenic effects on cultured human lymphocytes exposed to doxorubicin

Antunes, Lusânia Maria Greggi; Bueno, Rafaela de Barros e Lima; Dias, Francisca da Luz; Bianchi, María de Lourdes Pires

doi:10.1016/j.mrgentox.2006.09.009

Cited by 17 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The main mechanisms of action proposed for DOX include the inhibition of topoisomerase II, DNA intercalation, free radical formation, reductive bioactivation of the quinine ring to a semiquinone radical, DNA alkylation and cross-linking (Gewirtz, 1999;Ramji et al, 2003;Navarro et al, 2006). These mechanisms can result in the cleavage of DNA which, if not repaired, may lead to mutations and chromosomal aberrations in tumors as well as in healthy cells (Antunes and Takahashi, 1998;Gentile et al, 1998;Islaih et al, 2005;Antunes et al, 2007;Costa and Nepomuceno, 2006;Fragiorge et al, 2007;Valadares et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

et al. 2008

View full text Add to dashboard Cite

Panax ginseng is one of the most widely prescribed herbal medicines for the treatment of cancer, diabetes, chronic inflammation, and neurodegenerative and cardiovascular diseases. Since the use of alternative medicines in combination with conventional therapy may increase the risk of unwanted interactions, we investigated the possible genotoxicity of a water-soluble form of the dry root of P. ginseng (2.5, 5.0 or 10.0 mg/mL) and its ability to protect against the genotoxicity of doxorubicin (DOX; 0.125 mg/mL) by using the Drosophila melanogaster wing somatic mutation and recombination test (SMART) with standard and high-bioactivation crosses of flies. Panax ginseng was not genotoxic at the concentrations tested, whereas DOX-induced genotoxicity in marker-heterozygous flies resulted mainly from mitotic recombination. At low concentrations, P. ginseng had antirecombinogenic activity that was independent of the concentration of extract used. Recombination events may promote cancer, but little is known about the ability of P. ginseng to inhibit such recombination or modulate DNA repair mechanisms.

show abstract

Section: Introductionmentioning

confidence: 99%

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Furthermore, a significant reduction in total plasma antioxidant capacity was observed in smallcell lung cancer patients treated with DXR (Erhola et al, 1996). It is important to reduce the genotoxicity of DXR in non-tumor cells, a goal that has been achieved experimentally by concurrent administration of free radical scavengers such as antioxidants (Amara-Mokrane et al, 1996;Antunes and Takahashi, 1998;Gentile et al, 1998;Costa and Nepomuceno, 2006;Antunes et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

2007

Self Cite

View full text Add to dashboard Cite

In this study two different crosses involving the wing cell markers mwh and flr 3 (standard (ST) cross and high bioactivation (HB) cross, the latter being characterized by a high constitutive level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens) were used to investigate the modulatory effects of ascorbic acid (AA) combined with the antitumor agent doxorubicin (DXR) in Drosophila melanogaster. We observed that the two different concentrations of AA (50 or 100 mM) had no effect on spots frequencies, while DXR treatments (0.2 or 0.4 mM) gave positive results for all types of spots, when compared to negative control. For marker-heterozygous (MH) flies, a protective effect was observed with the lower concentration of AA (50 mM) that was able to statistically decrease the frequency of spots induced by DXR (0.2 mM), while an enhanced frequency of spots induced by DXR was observed with the higher concentration of AA (100 mM), when compared to DXR treatment (p < 0.05). These results suggest that AA may interfere with free radicals generated by DXR and with other possible reactive metabolites. The efficiency of AA in protecting the somatic cells of D. melanogaster against mutation and recombination induced by DXR is dependent on the dose used and the protection is directly related to the activity of cytochrome P450 enzymes.

show abstract

“…This result is expected, considering that PG induces ROS generation [39] and that ASA inhibits Cox-2 action, reversing this process. Antunes et al [9] found a inhibition in the total number of chromosomal aberrations and aberrant metaphases caused by ROS released by doxorubicin in lymphocytes incubated for 24 h with ASA (25, 50 or 100 μg/ml), which supports its role as an antioxidant agent.…”

Section: Discussionmentioning

confidence: 87%

“…The suppressive and protective effects of ASA as an antitumoral drug might be at least partially ascribed to its antioxidant properties. ASA may act as an antioxidant, inhibiting chromosomal damage induced by the free radicals generated by doxorubicin [9]. Also, Hsu and Li [10] demonstrated that the inhibition of oxidative stress by ASA is concentrationdependent in vitro, and it was proposed that the antioxidant activity of ASA might furnish cancer chemoprotection in humans.…”

Section: Introductionmentioning

confidence: 99%

Anti-MDR and antitumoral action of acetylsalicylic acid on leukaemic cells

et al. 2011

View full text Add to dashboard Cite

ASA (acetylsalicylic acid) is an NSAID (non-steroidal anti-inflammatory drug). ASA has gained attention as a potential chemopreventive and chemotherapeutic agent for several neoplasms. The aim of this study was to analyse the possible antitumoural effects of ASA in two erythroleukaemic cell lines, with or without the MDR (multidrug resistance) phenotype. The mechanism of action of different concentrations of ASA were compared in K562 (non-MDR) and Lucena (MDR) cells by analysing cell viability, apoptosis and necrosis, intracellular ROS (reactive oxygen species) formation and bcl-2, p53 and cox-2 gene expression. ASA inhibited the cellular proliferation or induced toxicity in K562 and Lucena cell lines, irrespective of the MDR phenotype. The ASA treatment provoked death by apoptosis and necrosis in K562 cells and only by necrosis in Lucena cells. ASA also showed antioxidant activity in both cell lines. The bcl-2, p53 and cox-2 genes in both cell lines treated with ASA seem to exhibit different patterns of expression. However, normal lymphocytes treated with the same ASA concentrations were more resistant than tumoral cells. The results of this work show that both cell lines responded to treatment with ASA, demonstrating a possible antitumoral and anti-MDR role for this drug.

show abstract

Acetylsalicylic acid exhibits anticlastogenic effects on cultured human lymphocytes exposed to doxorubicin

Cited by 17 publications

References 32 publications

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Anti-MDR and antitumoral action of acetylsalicylic acid on leukaemic cells

Contact Info

Product

Resources

About