Cytogenetic instability in populations with residential proximity to open-pit coal mine in Northern Colombia in relation to PM10 and PM2.5 levels.

Epidemiological studies indicate that living in proximity to coal mines is correlated with numerous diseases including cancer, and that exposure to PM10 and PM2.5 components could be associated with this phenomenon. However, the understanding of the mechanisms by which PM exerts its adverse effects is still incomplete and comes mainly from studies in occupationally exposed populations. The aims of this study were to: (1) evaluate DNA damage in lymphocytes assessing the cytokinesis-block micronucleus cytome assay (CBMN-cyt) parameters; (2) identify aneugenic or clastogenic effects in lymphocytes of exposed populations using CREST immunostaining for micronuclei; (3) evaluate multi-elemental composition of atmospheric particulate matter; and (4) verify relation between the DNA damage and PM2.5 and PM10 levels around the mining area. Analysis revealed a significant increase in micronuclei frequency in binucleated (MNBN) and mononucleated (MNMONO) cells of individuals with residential proximity to open-pit coal mines compared to residents from non-mining areas. Correlation analysis demonstrated a highly significant association between PM2.5 levels, MNBN frequencies and CREST+ micronuclei induction in exposed residents. These results suggest that PM2.5 fraction generated in coal mining activities may induce whole chromosome loss (aneuploidy) preferentially, although there are also chromosome breaks. Analysis of the chemical composition of PM2.5 by PIXE demonstrated that Si, S, K and Cr concentrations varied significantly between coal mining and reference areas. Enrichment factor values (EF) showed that S, Cr and Cu were highly enriched in the coal mining areas. Compared to reference area, mining regions had also higher concentrations of extractable organic matter (EOM) related to nonpolar and polar compounds. Our results demonstrate that PM2.5 fraction represents the most important health risk for residents living near open-pit mines, underscoring the need for incorporation of ambient air standards based on PM2.5 measures in coal mining areas.

Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats.

Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

Biological functions of selenium and its potential influence on Parkinson's disease.

Parkinson's disease is characterized by the death of dopaminergic neurons, mainly in the substantia nigra, and causes serious locomotor dysfunctions. It is likely that the oxidative damage to cellular biomolecules is among the leading causes of neurodegeneration that occurs in the disease. Selenium is an essential mineral for proper functioning of the brain, and mainly due to its antioxidant activity, it is possible to exert a special role in the prevention and in the nutritional management of Parkinson's disease. Currently, few researchers have investigated the effects of selenium on Parkinson´s disease. However, it is known that very high or very low body levels of selenium can (possibly) contribute to the pathogenesis of Parkinson's disease, because this imbalance results in increased levels of oxidative stress. Therefore, the aim of this work is to review and discuss studies that have addressed these topics and to finally associate the information obtained from them so that these data and associations serve as input to new research.

Method validation for determination of metals in Vitis labrusca L. grapevine leaf extracts by inductively coupled plasma mass spectrometry (ICP-MS).

Vitis labrusca L. is the main species used for wine and juice production in Brazil. The grapevine leaves can be used both as functional foods and as cheapest sources for the extraction of phenolic compounds. Besides the antioxidant activity, grapevine leaves exhibited significant anti-inflammatory activity. Therefore, the aim of this study was to develop and validate an analytical methodology to determine the metals selenium (96Se), chromium (53Cr), nickel (62Ni), cadmium (111Cd) and lead (206Pb) in 30 samples of grapevine leaf extracts (Vitis labrusca, Bordo cultivar) using inductively coupled plasma mass spectrometry (ICP-MS). To obtain the grapevine leaf extracts the samples were milled, weighed and digested in microwave oven with nitric acid. The method showed linearity, precision, accuracy and limits of quantification and detection acceptable for INMETRO protocol validation of analytical methods. Therefore, the method using ICP-MS was developed and validated to determine metals concentrations in grapevine leaves of Vitis labrusca L. and the proposed method could be applied in routine analytical laboratory.

Pharmacological perspectives from Brazilian Salvia officinalis (Lamiaceae): antioxidant, and antitumor in mammalian cells.

Salvia officinalis (Lamiaceae) has been used in south of Brazil as a diary homemade, in food condiment and tea-beverage used for the treatment of several disorders. The objective of this study was to characterize chemical compounds in the hydroalcoholic (ExtHS) and aqueous (ExtAS) extract from Salvia officinalis (L.) by gas chromatography-mass spectrometry (GC-MS) and by high-resolution electrospray ionization mass spectrometry (ESI-QTOF MS/MS), evaluate in vitro ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), catalase (CAT-like) and superoxide dismutase (SOD-like) activity, moreover cytotoxic by MTT assay, alterations on cell morphology by giemsa and apoptotic-induced mechanism for annexin V/propidium iodide. Chemical identification sage extracts revealed the presence of acids and phenolic compounds. In vitro antioxidant analysis for both extracts indicated promising activities. The cytotoxic assays using tumor (Hep-2, HeLa, A-549, HT-29 and A-375) and in non-tumor (HEK-293 and MRC-5), showed selectivity for tumor cell lines. Immunocytochemistry presenting a majority of tumor cells at late stages of the apoptotic process and necrosis. Given the results presented here, Brazilian Salvia officinalis (L.) used as condiment and tea, may protect the body against some disease, in particularly those where oxidative stress is involved, like neurodegenerative disorders, inflammation and cancer.

Investigation of potential biomarkers for the early diagnosis of cellular stability after the exposure of agricultural workers to pesticides.

Agricultural workers involved in the harvest of tobacco crops are regularly exposed to large quantities of pesticides. In order to determine how this exposure to pesticides induces genetic alterations in these workers, blood samples were obtained from 77 exposed individuals, as well as from 60 unexposed subjects. DNA damage was analyzed by the Comet assay and by the micronucleus (MN) test. The antioxidant profile was evaluated by activity of superoxide dismutase (SOD), and the polymorphism of gene PON1 was used as a susceptibility biomarker. The content of inorganic elements in the blood samples was determined by PIXE analysis. Our results demonstrated that the damage frequency, damage index, the MN frequency, and the SOD activity were significantly elevated in the exposed relative to the unexposed group. A modulation of the MN results for the PON1 gene was observed in the exposed group. The concentrations of inorganic elements in the exposed group were higher compared to those of the unexposed group. In this study, we observed that genetic damage, and change in oxidative balance were induced by the exposure of workers to complex mixtures of pesticides in the presence of inorganic compounds, whereby an influence of the genotype was evident.

Antigenotoxic and antimutagenic effects of diphenyl ditelluride against several known mutagens in Chinese hamster lung fibroblasts.

The present study evaluates antigenotoxic and antimutagenic properties of diphenyl ditelluride (DPDT) against several known mutagens in Chinese hamster lung fibroblasts (V79 cells). DPDT was not cytotoxic and genotoxic at concentrations ranging from 0.01 to 0.1 µM. The pre-treatment for 2h with this organotellurium compound at non-cytotoxic dose range (0.01, 0.05 and 0.1 µM) increased cell survival after challenge with hydrogen peroxide (H2O2), t-butyl hydroperoxide (t-BOOH), methylmethanesulphonate (MMS) or ultraviolet (UV)C radiation. In addition, the pre-treatment with DPDT decreased the DNA damage and Formamidopyrimidine DNA-glycosylase (Fpg)- and Endonuclease III (Endo III) sensitive sites induction by the studied genotoxic agents, as verified by comet assay and modified comet assay, respectively. The pre-treatment also reduced micronucleus frequency, revealing the protector effect of DPDT against MMS and UVC-induced mutagenesis. Our results demonstrate that DPDT-treated cells at concentration range of 0.01-0.1 µM do not change thiobarbituric acid reactive species (TBARS) levels and ROS generation. Moreover, DPDT pre-treatment at this concentration range decreases the ROS induction by H2O2 and t-BOOH treatment indicating antioxidant potential. On the other hand, concentrations higher than 0.1 µM increase TBARS formation and inhibited superoxide dismutase (SOD) activity, suggesting pro-oxidative effect of this compound at high concentrations. Our results suggest that DPDT presents antigenotoxic and antimutagenic properties at concentration range of 0.01-0.1 µM. The protection effect could be attributed to antioxidant capacity of DPDT at this concentration range in V79 cells.

Biflorin: an o-naphthoquinone of clinical significance.

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives.

Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione - AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione - AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl)-1,3-thiazolidine-2,4-dione - AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2,4-dione - AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin-eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways.

DNA alkylation damage and autophagy induction.

Many alkylating agents are used as chemotherapeutic drugs and have a long history of clinical application. These agents inflict a wide range of DNA damage resulting in a complex cellular response. After DNA damage, cells trigger a series of signaling cascades promoting cellular survival and cell cycle blockage which enables time for DNA repair to occur. More recently, induction of autophagy has been observed in cancer cells after treatment with different DNA-targeted anticancer drugs, including alkylating agents. Several studies have demonstrated that induction of autophagy after DNA damage delays apoptotic cell death and may therefore lead to chemoresistance, which is the limiting factor for successful chemotherapy. On the other hand, depending on the extent of damage and the cellular context, the induction of autophagy may also contribute to cell death. Given these conflicting results, many studies have been conducted to better define the role of autophagy in cancer cells in response to chemotherapy. In this review, we describe the main alkylating agents used in clinical oncology as well as the cellular response they evoke with emphasis on autophagy.

PARPs and the DNA damage response.

Adenosine diphosphate (ADP)-ribosylation is an important posttranslational modification catalyzed by a variety of enzymes, including poly (ADP ribose) polymerases (PARPs), which use nicotinamide adenine dinucleotide (NAD(+)) as a substrate to synthesize and transfer ADP-ribose units to acceptor proteins. The PARP family members possess a variety of structural domains, span a wide range of functions and localize to various cellular compartments. Among the molecular actions attributed to PARPs, their role in the DNA damage response (DDR) has been widely documented. In particular, PARPs 1-3 are involved in several cellular processes that respond to DNA lesions, which include DNA damage recognition, signaling and repair as well as local transcriptional blockage, chromatin remodeling and cell death induction. However, how these enzymes are able to participate in such numerous and diverse mechanisms in response to DNA damage is not fully understood. Herein, the DDR functions of PARPs 1-3 and the emerging roles of poly (ADP ribose) polymers in DNA damage are reviewed. The development of PARP inhibitors, their applications and mechanisms of action are also discussed in the context of the DDR.

Ataxia telangiectasia mutated- and Rad3-related kinase drives both the early and the late DNA-damage response to the monofunctional antitumour alkylator S23906.

Numerous anticancer agents and environmental mutagens target DNA. Although all such compounds interfere with the progression of the replication fork and inhibit DNA synthesis, there are marked differences in the DNA-damage response pathways they trigger, and the relative impact of the proximal or the distal signal transducers on cell survival is mainly lesion-specific. Accordingly, checkpoint kinase inhibitors in current clinical development show synergistic activity with some DNA-targeting agents, but not with others. In the present study, we characterize the DNA-damage response to the antitumour acronycine derivative S23906, which forms monofunctional adducts with guanine residues in the minor groove of DNA. S23906 exposure is accompanied by specific recruitment of RPA (replication protein A) at replication sites and rapid Chk1 activation. In contrast, neither MRN (Mre11-Rad50-Nbs1) nor ATM (ataxia-telangiectasia mutated), contributes to the initial response to S23906. Interestingly, genetic attenuation of ATR (ATM- and Ras3-related) activity inhibits not only the early phosphorylation of histone H2AX and Chk1, but also interferes with the late phosphorylation of Chk2. Moreover, loss of ATR function or pharmacological inhibition of the checkpoint kinases by AZD7762 is accompanied by abrogation of the S-phase arrest and increased sensitivity towards S23906. These findings identify ATR as a central co-ordinator of the DNA-damage response to S23906, and provide a mechanistic rationale for combinations of S23906 and similar agents with checkpoint abrogators.

Susceptibility to DNA damage in workers occupationally exposed to pesticides, to tannery chemicals and to coal dust during mining.

Our mutagenesis group has been studying with important economic drivers of our state, such as agriculture, the foot-wear and leather industry and open-cast coal mining. Working conditions in these sectors have potentially harmful to humans. The aim of these studies is to determine the health risk of workers by biomonitoring subjects exposed to genotoxic agents. The main results of our studies with vineyard farmers we observed a high rate of MN and DNA damage in individuals exposed to pesticides (p < 0.001). In addition, some effects of genetic polymorphisms in the modulation of MN results were observed in this group. Tobacco farmers were also evaluated at different crop times. The results showed a significant increase in the Damage index and frequency in tobacco farmers compared to the non-exposed group, for all crop times. The results for footwear and tannery workers showed a significant increase in the mean ID for the solvent-based adhesive (p < 0.001) group in comparison to the water-based adhesive group and control (p < 0.05). For open-cast coal mine workers, the EBCyt indicated a significant increase in nuclear bud frequency and cytokinetic defects in the exposed group compared to the non-exposed group (p < 0.0001). We were able to associate specific genetic susceptibility with each type of exposure and with the non-use or improper use of personal protection equipment and diet adequacy. These results show how important the continuous education of exposed workers is to minimizing the effect of the occupational exposure and the risk of disease associated with the work.

NAP prevents acute cerebral oxidative stress and protects against long-term brain injury and cognitive impairment in a model of neonatal hypoxia-ischemia.

Hypoxia-ischemia (HI) is a common cause of neonatal brain damage with lifelong morbidities in which current therapies are limited. In this study, we investigated the effect of neuropeptide NAP (NAPVSIPQ) on early cerebral oxidative stress, long-term neurological function and brain injury after neonatal HI. Seven-day-old rat pups were subjected to an HI model by applying a unilateral carotid artery occlusion and systemic hypoxia. The animals were randomly assigned to groups receiving an intraperitoneal injection of NAP (3 µg/g) or vehicle immediately (0 h) and 24 h after HI. Brain DNA damage, lipid peroxidation and reduced glutathione (GSH) content were determined 24 h after the last NAP injection. Cognitive impairment was assessed on postnatal day 60 using the spatial version of the Morris water maze learning task. Next, the animals were euthanized to assess the cerebral hemispheric volume using the Cavalieri principle associated with the counting point method. We observed that NAP prevented the acute HI-induced DNA and lipid membrane damage and also recovered the GSH levels in the injured hemisphere of the HI rat pups. Further, NAP was able to prevent impairments in learning and long-term spatial memory and to significantly reduce brain damage up to 7 weeks following the neonatal HI injury. Our findings demonstrate that NAP confers potent neuroprotection from acute brain oxidative stress, long-term cognitive impairment and brain lesions induced by neonatal HI through, at least in part, the modulation of the glutathione-mediated antioxidant system.

Effect of vitamin A treatment on superoxide dismutase-deficient yeast strains.

Vitamin A (Vit A) is widely suggested to be protective against oxidative stress. However, different studies have been demonstrated the pro-oxidant effects of retinoids in several experimental models. In this work, we used the yeast Saccharomyces cerevisiae as a model organism to study the Vit A effects on superoxide dismutase (SOD)-deficient yeast strains. We report here that Vit A (10, 20 and 40 mg/ml) decreases the survival of exponentially growing yeast cells, especially in strains deficient in CuZnSOD (sod1Delta) and CuZnSOD/MnSOD (sod1Deltasod2Delta). We also observed the protective effect of vitamin E against the Vit A-induced toxicity. Possible adaptation effects induced by sub-lethal oxidative stress were monitored by pre-, co- and post-treatment with the oxidative agent paraquat. The enzymatic activities of catalase (CAT) and glutathione peroxidase (GPx), and the total glutathione content were determined after Vit A treatment. Our results showed that CuZnSOD represents an important defence against Vit A-generated oxidative damage. In SOD-deficient strains, the main defence against Vit A-produced reactive oxygen species (ROS) is GPx. However, the induction of GPx activity is not sufficient to prevent the Vit A-induced cell death in these mutants in exponential phase growth.

Evaluation of the cytotoxic and antimutagenic effects of biflorin, an antitumor 1,4 o-naphthoquinone isolated from Capraria biflora L.

Biflorin is a natural quinone isolated from Capraria biflora L. Previous studies demonstrated that biflorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration-dependent cytotoxic, genotoxic, antimutagenic, and protective effects of biflorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using different approaches. In the Salmonella/microsome assay, biflorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biflorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biflorin did not induce significant mutagenic and recombinogenic effects at the employed concentration range. In addition, the pre-treatment with biflorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H(2)O(2)) in S. cerevisiae. In V79 mammalian cells, biflorin was cytotoxic at higher concentrations. Moreover, at low concentrations biflorin pre-treatment protected against H(2)O(2)-induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modified comet assay using DNA glycosylases. Our results suggest that biflorin cellular effects are concentration dependent. At lower concentrations, biflorin has significant antioxidant and protective effects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H(2)O(2) in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biflorin is cytotoxic and genotoxic.

Macro and micro minerals: are frozen fruits a good source?

Fruits are rich in minerals, which are essential for a wide variety of metabolic and physiologic processes in the human body. The use of frozen fruits has greatly spread in the last years not only in the preparation of juices, but also as raw material for yogurts, candies, cookies, cakes, ice creams, and children's food. However, up to now there is no data about the mineral profile of frozen fruits. This is the first database to quantify the levels of minerals in 23 samples of frozen fruits, including the most used around the world and some native fruits from the Amazon rainforest in Brazil. Considering the Dietary Reference Intakes, 100g of frozen fruits can provide 0.2 to 2.8% of macro and 2.5 to 100% of microminerals for adults (31-50 years old). Although geographical differences should be considered, these data can help to plan diets and to develop population interventions aiming to prevent chronic diseases.

NAP prevents hippocampal oxidative damage in neonatal rats subjected to hypoxia-induced seizures.

Neonatal seizures in which hypoxic-ischemic encephalopathy is the main triggering etiology have a challenging diagnosis and limited efficacy of treatment. NAP (NAPVSIPQ) has shown extensive neuroprotective and antioxidant capacity in vitro and in vivo. To evaluate its neuroprotective role in the context of seizures associated with perinatal hypoxia, we assessed the integrity of DNA and lipid membranes as well as the redox status in the hippocampus of 10-day-old rats exposed to hypoxia-induced seizures (HS) with and without NAP treatment. Rats were exposed to transient global hypoxia (12 min exposure to 5-7% O2 was able to induce electrographic seizures) or room air with subsequent intraperitoneal NAP (0.03, 0.3 or 3 microg/g) or vehicle administration. Results showed elevated DNA damage immediately after the insult until 72 h post-HS, while oxidized bases were only detected 3, 6 and 24 h later. In addition, thiobarbituric acid reactive species peaked at 6 h in parallel with decreased levels of reduced glutathione between 3 and 72 h post-HS insult. Our findings expand on the knowledge about the time course of HS-induced oxidative damage and demonstrate for the first time that a single NAP injection dose-dependently prevents HS-induced oxidative damage to DNA and lipid membranes, in correlation with modulation of the glutathione system. Hence, NAP may represent a promising therapeutic strategy for avoiding HS-induced oxidative damage.

Dipyridamole as a new drug to prevent Epstein-Barr virus reactivation.

Epstein-Barr virus (EBV) is a widely distributed gamma-herpesvirus that has been associated with various cancers mainly from lymphocytic and epithelial origin. Although EBV-mediated oncogenesis has been associated with viral oncogenes expressed during latency, a growing set of evidence suggested that antiviral treatments directed against EBV lytic phase may contribute to prevent some forms of cancers, including EBV-positive Post-Transplant Lymphoproliferative Diseases. It is shown here that dipyridamole (DIP), a safe drug with favorable and broad pharmacological properties, inhibits EBV reactivation from B-cell lines. DIP repressed immediate early and early genes expression mostly through its ability to inhibit nucleoside uptake. Considering its wide clinical use, DIP repurposing could shortly be evaluated, alone or in combination with other antivirals, to treat EBV-related diseases where lytic replication plays a deleterious role.

Diphenyl Ditelluride: Redox-Modulating and Antiproliferative Properties.

Tellurium is a rare element that has been regarded as a toxic, nonessential element, and its biological role is not clearly established. In addition, the biological effects of elemental tellurium and some of its organic and inorganic derivatives have been studied, leading to a set of interesting and promising applications. Diphenyl ditelluride (DPDT), an organic tellurium derivate, showed antioxidant, antigenotoxic, antimutagenic, and anticancer properties. The antioxidant and prooxidant properties of DPDT are complex and depend on experimental conditions, which may explain the contradictory reports of these properties. In addition, DPDT may exert its effects through different pathways, including distinct ones to those responsible for chemotherapy resistance phenotypes: transcription factors, membrane receptors, adhesion, structural molecules, cell cycle regulatory components, and apoptosis pathways. This review aims to present recent advances in our understanding of the biological effects, therapeutic potential, and safety of DPDT treatment. Moreover, original results demonstrating the cytotoxic effects of DPDT in different mammalian cell lines and systems biology analysis are included, and emerging approaches for possible future applications are inferred.