Apigenin is a natural flavonoid found in several dietary plant foods such as vegetables and fruits. A large number of studies conducted over the past years have shown that this particular natural ...compound has potential antioxidant, anti-inflammatory, and anticancer properties. Therefore, apigenin has generated a great deal of interest as a possible chemotherapeutic modality due to its low intrinsic toxicity and remarkable effects on normal versus cancerous cells, compared with other structurally related flavonoids. Here, we review its role in anticancer research, as well as several cancer signalling pathways, including MAPK, PI3K/Akt and NF-κB pathways, and their specific role in different cancer types. Based on the available literature, the beneficial effects of apigenin as a future anticancer modality are promising but they require further in vitro and in vivo studies to enable its translation from bench to bedside.
•Apigenin is found in several dietary plant foods such as vegetables and fruits.•Apigenin has potential antioxidant, anti-inflammatory, and anticancer properties.•Apigenin could be used as a future anticancer modality.•Further studies are needed to enable its translation from bench to bedside.
Apigenin is found in several dietary plant foods such as vegetables and fruits. To investigate potential anticancer properties of apigenin on human breast cancer, ER-positive MCF-7 and ...triple-negative MDA MB-231 cells were used. Moreover, toxicological safety of apigenin towards normal cells was evaluated in human lymphocytes. Cytotoxicity of apigenin towards cancer cells was evaluated by MTT assay whereas further genotoxic and oxidative stress parameters were measured by comet and lipid peroxidation assays, respectively. In order to examine the type of cell death induced by apigenin, several biomarkers were used. Toxicological safety towards normal cells was evaluated by cell viability and comet assays. After the treatment with apigenin, we observed changes in cell morphology in a dose- (10 to 100 μM) and time-dependent manner. Moreover, apigenin caused cell death in both cell lines leading to significant toxicity and dominantly to apoptosis. Furthermore, apigenin proved to be genotoxic towards the selected cancer cells with a potential to induce oxidative damage to lipids. Of great importance is that no significant cytogenotoxic effects were detected in normal cells. The observed cytogenotoxic and pro-cell death activities of apigenin coupled with its low toxicity towards normal cells indicate that this natural product could be used as a future anticancer modality. Therefore, further analysis to determine the exact mechanism of action and in vivo studies on animal models are warranted.
Residues of anti-neoplastic drugs represent new and emerging pollutants in aquatic environments. Many of these drugs are genotoxic, and it has been postulated that they can cause adverse effects in ...aquatic ecosystems. 5-Fluorouracil (5-FU) is one of the most extensively used anti-neoplastic drugs in cancer therapy, and this article describes the results of the first investigation using a two-generation toxicity study design with zebrafish (Danio rerio). Exposure of zebrafish to 5-FU (0.01, 1.0 and 100 μg/L) was initiated with adult zebrafish (F0 generation) and continued through the hatchings and adults of the F1 generation, and the hatchings of the F2 generation, to day 33 post-fertilisation. The exposure did not affect survival, growth and reproduction of the zebrafish; however, histopathological changes were observed in the liver and kidney, along with genotoxic effects, at all 5-FU concentrations. Increases in DNA damage determined using the comet assay were significant in the liver and blood cells, but not in the gills and gonads. In erythrocytes, a significant, dose-dependent increase in frequency of micronuclei was observed at all 5-FU concentrations. Whole genome transcriptomic analysis of liver samples of F1 generation zebrafish exposed to 0.01 μg/L and 1 μg/L 5-FU revealed dose-dependent increases in the number of differentially expressed genes, including up-regulation of several DNA-damage-responsive genes and oncogenes (i.e., jun, myca). Although this chronic exposure to environmentally relevant concentrations of 5-FU did not affect the reproduction of the exposed zebrafish, it cannot be excluded that 5-FU can lead to degenerative changes, including cancers, which over long-term exposure of several generations might affect fish populations. The data from this study contribute to a better understanding of the potential consequences of chronic exposure of fish to low concentrations of anti-neoplastic drugs, and they demonstrate that further studies into multi-generation toxicity are needed.
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•Residues of anti-neoplastic drugs are emerging pollutants in aquatic environments.•Missing chronic ecotoxicity data constitute a critical knowledge gap.•Zebrafish two-generation chronic toxicity study of 5-FU was performed.•Genotoxic effects were detected at environmental concentrations.•Gene expression analysis revealed up-regulation of oncogenes.
The aim of this study is to investigate the radioprotective effect of bee venom against DNA damage induced by 915-MHz microwave radiation (specific absorption rate of 0.6 W/kg) in Wistar rats. Whole ...blood lymphocytes of Wistar rats are treated with 1 μg/mL bee venom 4 hours prior to and immediately before irradiation. Standard and formamidopyrimidine-DNA glycosylase (Fpg)–modified comet assays are used to assess basal and oxidative DNA damage produced by reactive oxygen species. Bee venom shows a decrease in DNA damage compared with irradiated samples. Parameters of Fpg-modified comet assay are statistically different from controls, making this assay more sensitive and suggesting that oxidative stress is a possible mechanism of DNA damage induction. Bee venom is demonstrated to have a radioprotective effect against basal and oxidative DNA damage. Furthermore, bee venom is not genotoxic and does not produce oxidative damage in the low concentrations used in this study.
Imatinib mesylate (IM) is the first developed protein kinase inhibitor and recently it has topped consumption rates among targeted and total anticancer drugs. Although there are indications that IM ...possesses cyto/genotoxic activities against normal non-target cells as well, there is a lack of information regarding the underlying mechanism involved in those actions. Therefore, we aimed to evaluate the response of human circulating blood cells towards oxidative stress after IM treatment (0.0001–10 µg/mL) in vitro. Based on the results, IM had an influence on all of the oxidative stress parameters tested. Lower concentrations of IM induced an increase of glutathione level, following its decrease at higher IM concentrations indicating impairment in oxidative stress defences. Concomitant to a glutathione decrease, an increase of malondialdehyde and protein carbonyls level was observed indicating oxidative damage of lipids and proteins. The observed effects overlapped with the observed formation of oxidative base damage detected by formamidopyrimidine-DNA glycosylase modified-comet assay indicating that IM managed to induce oxidative DNA damage. Our results provide novelty in their mechanistic approach to IM-induced toxicity in non-target cells and suggest that IM can affect blood cells and induce oxidative stress.
Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention and treatment of Plasmodium falciparum malaria. As safe and effective antimalarial drugs are needed in ...both the treatment and the prophylaxis of malaria, this study was performed to investigate their possible cyto/genotoxic potential towards human lymphocytes and the possible mechanism responsible for it. Two different concentrations of ATO and PROG were used with and without S9 metabolic activation. The concentrations used were those found in human plasma when a fixed‐dose combination of ATO and PROG was used: 2950/130 ng/mL after prophylactic treatment and 11 800/520 ng/mL after treatment of malaria, respectively. Possible cellular and DNA‐damaging effects were evaluated by cell viability and alkaline comet assays, while oxidative stress potential was evaluated by formamidopyrimidine‐DNA glycosylase (Fpg)‐modified comet assay, in addition to measuring malondialdehyde and glutathione levels. According to our results, the ATO/PROG combination displayed only weak cyto/genotoxic potential towards human lymphocytes with no impact on oxidative stress parameters, suggesting that oxidative stress is not implicated in their mechanism of action towards human lymphocytes. Given that the key portion of the damaging effects was induced after S9 metabolic activation, it is to presume that the principal metabolite of PROG, cycloguanil, had the greatest impact. The obtained results indicate that the ATO/PROG combination is relatively safe for the consumption from the aspect of cyto/genotoxicity, especially if used for prophylactic treatment. Nevertheless, further cytogenetic research and regular patient monitoring are needed to minimize the risk of adverse events especially among frequent travellers.
► Human blood was exposed to low concentrations of DDT, DDE and DDD. ► Those concentrations proved to be genotoxic, although not inducing oxidative damage. ► Increase in micronucleus test parameters ...was also observed. ► Use of DDT pose threat to humans and it should be replaced with other pesticides.
Despite that the use of DDT has been restricted for more than 40 years to malaria affected areas, low doses of this pesticide and its metabolites DDE and DDD can be found in the environment around the world. Although it has been shown that these pollutants induce cell and DNA damage, the mechanisms of their cytogenotoxic activity remains largely unknown. This study looks into their possible genotoxic effects, at doses that can be found in body fluids, on human lymphocytes using the cytokinesis-block micronucleus assay and the comet assay. After exposure for 1, 6, and 24h compounds p,p′-DDT (0.1μgmL−1), p,p′-DDE (4.1μgmL−1), and p,p′-DDD (3.9μgmL−1) showed increase in DNA damage. The most significant results were observed at exposure period of 24h where number of micronucleated cells increased from control 2.5±0.71 to 23.5±3.54, 13.5±0.71, and 16.5±6.36 for DDT, DDE, and DDD, respectively. Similar effect was observed using comet test where the percentage of DNA in comets tail increased from control 1.81±0.16 to 17.24±0.55, 11.21±0.56 and 9.28±0.50 for each compound, respectively. At the same time Fpg-comet assay failed to report induction of oxidative DNA damage of these pollutants. Additionally, the type of cell death was determined using diffusion assay and necrosis dominated. Our findings suggest that even at low concentrations, these pesticides could induce cytogenetic damage to human peripheral blood lymphocytes and in that manner have the impact on human health as well.
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•Health-related biomarkers in vegetarians vs. non-vegetarians were assessed.•Results revealed differences in biomarkers between the two groups.•Supplementation of animal derived ...nutrients to vegetarians would be beneficial.•Evaluated biomarkers give insight into dietary preferences and health outcomes.
This study was performed in a group of adult vegetarians (N = 40) and matched non-vegetarian subjects (N = 40) in order to analyse differences in health-related biomarkers. Obtained results revealed differences in various biomarkers between subjects on a traditional mixed and vegetarian diet, indicating that vegetarians have a lower nutritional status of some nutrients (Ca, Cu and Zn, and vitamins B12 and D) accompanied with a lower antioxidant defence system (glutathione) and higher homocysteine and genome damage (micronuclei and DNA strand breaks), along with shorter telomeres. This suggests that the supplementation of animal derived nutrients to this particular dietary group would be beneficial for the improvement of some measured health-related biomarkers. However, the level of certain toxic metals (As and Hg) was higher in non-vegetarians. The presented multi-biomarker approach implies the necessity of evaluating a large number of different health-related biomarkers in order to obtain clear insight into dietary preferences and health outcomes.
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