Different duration of exposure to a pulsed magnetic field can cause changes in mRNA expression of apoptotic genes in oleic acid-treated neuroblastoma cells.

PURPOSE: Neuroblastoma, a prevalent childhood tumor, poses significant challenges in therapeutic interventions, especially for high-risk cases. This study aims to fill a crucial gap in our understanding of neuroblastoma treatment by investigating the potential molecular impacts of short- and long-term pulsed magnetic field exposure on the neuronal apoptosis mechanism in an in vitro model of neuroblastoma treated with oleic acid (OA). MATERIALS AND METHODS: Cells were cultured and divided into six following experimental groups: (I) Nontreated group (NT); (II) OA-treated group (OA); (III) Group treated with OA after being exposed to the pulsed magnetic field for 15-min (15 min PEMF + OA); (IV) Group treated with OA after being exposed to the pulsed magnetic field for 12 h (12 h PEMF + OA); (V) Group exposed to the pulsed magnetic field for 15 min (15 min PEMF); and (VI) Group exposed to the pulsed magnetic field for 12 h (12 h PEMF). Cell viability, rates of apoptosis, and mRNA levels of key apoptotic genes (TP53, Bcl2, Bax, and Caspase-3) were assessed. RESULTS: Significant reductions in cell viability were observed, particularly in the group treated with OA following long-term pulsed magnetic field exposure. Flow cytometry revealed elevated apoptosis rates, notably in the early stages of apoptosis. qRT-PCR analysis demonstrated increased expression of cleaved Caspase-3, Bax/Bcl2 ratio, and TP53 in cells treated with OA following long-term pulsed magnetic field exposure, signifying enhanced apoptotic pathways. CONCLUSIONS: The findings indicate that long-term pulsed magnetic field exposure and OA treatment exhibit potential synergistic effects leading to the induction of apoptosis in SH-SY5Y cells. We have concluded that stimulations of pulsed magnetic field have the potential to serve as an adjuvant therapy for oleic acid-based treatment of neuroblastoma.

7,8-Dihydroxy Flavone Induces Apoptosis via Upregulation of Caspase-3 in Human Hepatocarcinoma Cell.

OBJECTIVE: 7,8-Dihydroxyflavone, a tyrosine kinase receptor agonist, is a flavonoid that has recently gained the attention of researchers due to its anticancer properties. Nevertheless, molecular pathways of 7,8-dihydroxyflavone for hepatocarcinoma are uncertain. Our aim was to identify the impact of 7,8-dihydroxyflavone on human hepatocarcinoma. MATERIAL AND METHODS: Human hepatocarcinoma cell line-7 cells were used as human hepatocarcinoma cells, and 7,8-dihydroxyflavone was applied to the cells at various doses. The cytotoxic and apoptotic effects of 7,8-dihydroxyflavone were determined with Alamar Blue and flow cytometry. The properties of 7,8-dihydroxyflavone on the mRNA expressions related with Bcl-2, Bax, cleaved-caspase-3 genes, and protein expressions were determined via quantitative real-time polymerase chain reaction and western blot analysis, respectively. RESULTS: 7,8-Dihydroxyflavone-enhanced cell death in human hepatocarcinoma cell line-7 via the overexpression of cleaved-caspase-3 (P=.003) and decreased Bcl-2 (P=.038) protein levels. Furthermore, cleavedcaspase-3 mRNA overexpression (P=.001) markedly led to 7,8-dihydroxyflavone-induced apoptosis. CONCLUSION: 7,8-Dihydroxyflavone could promote apoptotic cell death by modulating caspase pathways and suppressing antiapoptotic protein. These characteristics may mediate to clinical practice of 7,8-dihydroxyflavone for prevention and therapy of hepatocarcinoma.

Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer.

Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors.Communicated by Ramaswamy H. Sarma.

Cytoprotective effects of low-frequency pulsed electromagnetic field against oxidative stress in glioblastoma cells.

The low-frequency pulsed electromagnetic field (PEMF) may have possible cytoprotective effects against the destructive effects of oxidative stress. The goal was to investigate if shortterm low-frequency PEMF has cytoprotective effects in glioblastoma cell line following high-dose hydrogen peroxide (H2O2) treatment. U87-MG cells were divided into four groups: Sham-control group; PEMF group (cells exposed to PEMF); H2O2 group (cells treated with H2O2 at time intervals 30 min and 48 h, respectively); H2O2+PEMF group (cells exposed to PEMF after H2O2 treatment at time intervals 30 min and 48 h, respectively). The cell viability, levels of reactive oxygen species, glutathione peroxidase activity, and the amount of glutathione were measured. The cytoprotective effect of PEMF against deleterious effects of oxidative stress triggered by different time interval of H2O2 treatment might be mediated by the increase in the cell viability, the elevation in the antioxidant enzyme activity/amount, and the decrease in the reactive oxygen species level. In addition, the cytoprotective effect of PEMF varies depending on different time intervals of H2O2 treatment. In the light of these findings, further in vivo and/or in vitro studies on neurophysiological effects of PEMFs and their underlying molecular mechanisms are needed to elucidate neurotoxic or neuroprotective role against antioxidant defense mechanisms.

Cytotoxic, Apoptotic, and Oxidative Effects of Preserved and Preservative-Free Brimonidine in a Corneal Epithelial Cell Line.

Purpose: This study aims to compare the cytotoxic, apoptotic, and oxidative effects of preserved and preservative-free forms of brimonidine 0.15% on the human corneal epithelial cell (HCEC) line. Methods: Time-dependent cytotoxicity studies were performed with the Alamar Blue method. For apoptotic studies, PE Annexin V and 7-amino-actinomycin (7-AAD) staining and flow cytometry were performed. Messenger RNA (mRNA) expressions of Bax, Bcl-2, and caspase-3, -9, -12, and protein expressions of Bax and Bcl-2 were evaluated by quantitative real-time polymerase chain reaction and Western blot method, respectively. Results: Cell viability was 76.4% with the preserved solution and 36.05% with the preservative-free solution at the fifth minute. No significant difference was observed with either solution at the 15-min mark, whereas cell viability did not change significantly after 1 h. In the apoptosis evaluation, it was observed that the preservative-free solution increased the early apoptotic activity to a greater degree (P < 0.05). Preservative-free solution also induced gene expression of proapoptotic Bax, caspase-9 and -12, and protein expression of Bax while reducing the protein expression of anti-apoptotic Bcl-2 (P < 0.0001). Preserved solution induced only the gene expression of caspase-12, and reduced the protein expression of Bcl-2 (P < 0.0001). No significant difference was observed in the reactive oxygen species (ROS) levels of either solution compared with the control group (P > 0.05). Conclusion: It was demonstrated that the preserved solution is less cytotoxic to the HCEC line in the early period, has less early apoptotic activity, and does not significantly increase ROS levels.

Artichoke for biochemistry, histology, and gene expression in obstructive jaundice

SUMMARY OBJECTIVE: This study aimed to evaluate the hepatoprotective effect of artichoke leaf extract (Cynara scolymus) in experimental obstructive jaundice. METHODS: Rats were separated into three groups, namely, sham, control, and artichoke leaf extract. Ischemia was created for 60 min, and then liver tissue and blood samples were taken at the 90th minute of reperfusion. Artichoke leaf extract was given at a 300 mg/kg dose 2 h before the operation. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum. Histopathological findings of the liver were scored semiquantitatively. RESULTS: Antioxidant enzyme activities in the artichoke leaf extract group were statistically significantly higher than that in the other two groups. Biochemical parameters, which show hepatocellular damage, were found to be similar in both sham and artichoke leaf extract groups. Although the values in the sham group were higher than the artichoke group in terms of protein and gene expressions, no statistically significant difference was found between these two groups. Regarding the hepatocellular effects of obstructive jaundice, the artichoke leaf extract group showed lower scores than the control group in all histopathological scores. CONCLUSION: The results of this study showed that artichoke leaf extract had a hepatoprotective effect that was associated with the antioxidant and anti-inflammatory effects of artichoke leaf extract.

Effects of artichoke leaf extract on hepatic ischemia-reperfusion injury

SUMMARY OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effect and mechanism of action of artichoke leaf extract in hepatic ischemia/reperfusion injury. METHODS: Rats were divided into three groups such as sham, control, and artichoke leaf extract groups. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum obtained from the subjects. Histopathological findings were scored semiquantitatively. RESULTS: Statistically, the antioxidant activity was highest in the artichoke leaf extract group, the difference in biochemical parameters and C-reactive protein was significant compared with the control group, and the histopathological positive effects were found to be significantly higher. CONCLUSIONS: As a result, artichoke leaf extract had a hepatoprotective effect and that this effect was related to the antioxidant and anti-inflammatory effects of artichoke.

Synthesis of Silica Based Nanoparticles Against the Proliferation of Human Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) has the second-highest morbidity and mortality rates in men. Possessing facile surface chemistry and unique optical properties make silica nanoparticles(SiO2-NPs) promising cancer therapy materials. OBJECTIVE: This study aimed to investigate the effects of SiO2-NPs and their derivatives, including SiNP-NH2, SiNP-Cl, and SiNP-SH against PCa and clarify their molecular mechanism on cell death, gene, and protein expressions. METHODS: Following the synthesis and derivation of SiO2-NPs, their characterization was carried out using TEM, DLS, BET, and FT-IR. Cytotoxic properties of the compounds were investigated against different human cancerous cells; including HUH-7, A549, DLD-1, HeLa, NCI-H295R, and PC-3, as well as human healthy epithelium cell line PNT1A. RESULTS: SiNP-NH2, SiNP-Cl, and SiNP-SH dose-dependently inhibited the proliferation of PC-3 cells with an IC50 value as 55.46 µg/mL, 55.09 µg/mL and 72.89 µg/mL, respectively. SiNP-SH significantly(p<0.0001) inhibited metastasis and invasion of PC-3 cells(20.4% and 46.7%, respectively), and significantly(p<0.0001) increased early apoptosis(32.3%) when compared with non-treated cells. Protein and mRNA expressions of BcL-2, Bax, caspase-3, caspase-9, caspase-12, p53, Smad-4, Kras, and Nf-ĸB were also altered following the treatment of SiO2-NPs and its derivatives. CONCLUSION: Our results demonstrated that -SH functioned SiO2-NPs can prevent the proliferation of human PCa by increasing apoptosis by up-regulating gene and protein expression of p53(TP53) as well as caspase-3, caspase-9, and caspase-12 in the apoptotic pathway. Besides, the increased level of Smad-4 has also implicated the decreased cell proliferation. Hence, low sized SiNP-SH nanoparticles might be a suitable candidate for the treatment of human PCa.

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma.

The present study's objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with IC 50 values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L-1. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (p < 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (p < 0.001), which leads the cells to trigger apoptosis. In conclusion, the present in vitro study may supply a significant background for in vivo studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify.

Encapsulation of Small Drugs in a Supramolecule Enhances Solubility, Stability, and Therapeutic Efficacy Against Glioblastoma Multiforme.

Cancer occupies a high rank in the global morbidity and mortality scale with glioblastoma multiforme (GBM) accounting for almost 80% of all primary tumors of the brain. Despite the increasing availability of targeted and immunotherapeutic agents, chemotherapy still plays an important role in the treatment of neoplastic diseases. Limitations to the effective use of chemotherapy such as low aqueous solubility and high toxicity have directed the scientific community's interest to the development of new therapeutic agents with enhanced efficacy and limited toxicity. Supramolecular chemistry has offered an alternative way on the design and development of new therapeutic agents as a result of their unique properties. Supramolecules can be used as drug carriers since their cavities can host a wide range of small drugs and surpass in this way the drawbacks of current therapeutic agents. Herein, we present the principles that should be followed for the encapsulation of small drugs in supramolecules with enhanced physicochemical properties and increased efficacy against glioblastoma multiforme.

Possible effects of different doses of 2.1 GHz electromagnetic radiation on learning, and hippocampal levels of cholinergic biomarkers in Wistar rats.

The present study evaluated whether short-term exposure to different doses of 2.1 GHz radiofrequency electromagnetic radiation (RF-EMR) has different effects on rats' behaviour and hippocampal levels of central cholinergic biomarkers. Animals were divided into three equal groups namely; group 1 was sham-exposed group, group 2-3 were exposed to 45 V/m and 65 V/m doses of 2.1 GHz frequency for 1 week respectively. Numerical dosimetry simulations were carried out. Object location and Y-maze were used as behavioural tasks. The protein and mRNA expression levels of AChE, ChAT, and VAChT, in the hippocampus were tested using Western Blotting and Real-Time PCR. The impairment performance of rats subjected to 65 V/m dose of 2.1 GHz RF-EMR in both object location and Y-maze tasks was observed. The hippocampal levels of AChE, ChAT, and VAChT, were significantly lower in rats exposed to 65 V/m dose of 2.1 GHz RF-EMR than others. The stronger effect of "65 V/m" dose on both rat's hippocampal-dependent behavioural performances and hippocampal levels of cholinergic biomarkers may be due to the stronger effect of "65 V/m" dose where rats' snouts were located at the nearest distance from the monopole antenna. Furthermore, the simulated SAR values were high for 65 V/m electric-field strengths. For the first time, we report the potential dose-dependent effects of short-term exposure to 2.1 GHz radiation on rat's behavioural performances as well as hippocampal levels of cholinergic biomarkers. Further studies are needed to understand the mechanisms by which RF-EMR influences the function of the central cholinergic system in the brain.

Comparison of anticarcinogenic properties of Viburnum opulus and its active compound p-coumaric acid on human colorectal carcinoma.

Resistance to therapeutic agents and the highly toxic side effects of synthetic drugs has spurred new research in the treatment of colon cancer, which has high morbidity and mortality ratios. This study aims to clarify the molecular mechanisms of the anticarcinogenic properties of methanol extract of Viburnum opulus L. (EVO)and its main active compound, trans-p -coumaric acid ( p -CA), on human colon cancer cells (DLD-1, HT-29, SW-620, Caco-2) and healthy colon epithelial cells (CCD-18Co). The effects of EVO on controlled cell death (apoptosis) and the cell division cycle were determined by flow cytometry. Alteration in mRNA and protein expressions of switch genes in colorectal carcinoma (APC, MLH1, TP53, SMAD4, KRAS, and BRAF) were determined by qRT-PCR and Western blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLC analyses prove that p -CAis the main compound of EVO. EVO and p -CA inhibit the proliferation of human colon cancer cells DLD-1 and HT-29 in a dose-dependent manner. EVO increases apoptosis of DLD-1 cells and halts the cell cycle in the G2 stage in HT-29 cells. mRNA and protein expressions of p53 and SMAD-4 are upregulated, while BRAFs are downregulated. The results were directly proportional to p -CA. EVO and p -CA up- and downregulate switch genes and protein expressions of DLD-1 cells, which alter the expression of 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effects may be due to the presence of p -CA.

Thiazolidine based fluorescent chemosensors for aluminum ions and their applications in biological imaging.

Utilization of fluorescent techniques in detection of various metal ions actively pursued allow ultrasensitive and selective detections of metal ions and prevent the adverse effect of cations such as aluminum (III) ions. In this study, two novel fluorescent chemosensors containing thiazole derivatives, ((E)-2-(4-hydroxy-3-(((2-hydroxyphenyl)imino)methyl)phenyl)-3-phenyl thiazolidin-4-one) AM1 and (2,3-bis(4-hydroxy-3-((E)-((2-hydroxyphenyl)imino) methyl) phenyl) thiazolidin-4-one) AM2, have been fabricated. The probes AM1 and AM2 were prepared using the condensation reaction between 2-hydroxy-5-(4-oxo-3-phenyl thiazolidin-2-yl) benzaldehyde and 2-aminophenol for the probe AM1 and 5,5'-(4-oxothiazolidine-2,3-diyl)bis(2-hydroxy benzaldehyde) and 2-aminophenol for the probe AM2. Afterwards, they were analyzed by various types of NMR and FT-IR spectroscopy, ESI-MS spectra, and elemental anayzer. As a second step, each fabricated chemosensor was able to use turn on fluorescence sensing for detecting of Al3+ ions in ACN/H2O (v/v = 50/50, 10.0 µM, pH = 7.0) solution. Clear complexes formed between the probe AM1 and Al3+ ions and also the probe AM2 and Al3+ ions was determined by not only 1H NMR titration study but also calculated by using the Job's plot. The limit of detection (LOD) value was found to be 0.11 µM (AM1) and 4.4 µM (AM2) for Al3+ ions. Likewise, cell imaging and in vitro cytotoxicity experiments of Al3+ ions in Human epithelium Lovo cells exhibited that prepared chemosensors had low cytotoxicity and blue fluorescence when they treated with of Al3+ ions in the cellular system.

Formation of the inclusion complex of water soluble fluorescent calix[4]arene and naringenin: solubility, cytotoxic effect and molecular modeling studies.

Naringenin is considered as an important flavonoid in phytochemistry because of its important effect on cancer chemoprevention. Unfortunately its poor solubility has restricted its therapeutic applications. In this study, an efficient water-soluble fluorescent calix[4]arene (compound 5) was synthesized as host macromolecule to increase solubility and cytotoxicity in cancer cells of water-insoluble naringenin as well as to clarify localization of naringenin into the cells. Complex formed by host-guest interaction between compound 5 and naringenin was analyzed with UV-visible, fluorescence, FTIR spectroscopic techniques and molecular modeling studies. Stern-Volmer analysis showed binding constant value of Ksv 3.5 × 107 M-1 suggesting strong interaction between host and guest. Binding capacity shows 77% of naringenin was loaded on compound 5. Anticarcinogenic effects of naringenin complex were evaluated on human colorectal carcinoma cells (DLD-1) and it was found that 5-naringenin complex inhibits proliferation of DLD-1 cells 3.4-fold more compared to free naringenin. Fluorescence imaging studies show 5-naringenin complex was accumulated into the cytoplasm instead of the nucleus. Increased solubility and cytotoxicity of naringenin with fluorescent calix[4]arene makes it one of the potential candidates as a therapeutic enhancer. For deep understanding of host-guest interaction mechanisms, complementary multiscale molecular modeling studies were also carried out.Communicated by Ramaswamy H. Sarma.

Synthesis and evaluation of the antitumor activity of Calix[4]arene l-proline derivatives.

The unique conformational properties, functionality, low toxicity, and low cost make calixarene-based compounds a valuable candidate against cancer. The aim of the present study is the synthesis of the upper rim and lower rim-functionalized l-proline-based calix[4]arene derivatives and evaluation of their cytotoxic potential for human cancerous cells as well as to determine the death mechanism. Synthesized calix[4]arene (3, 8a, 8b 13a, and 13b) derivatives were characterized by different spectroscopic techniques such as 1HNMR, 13CNMR, and FTIR. In vitro effects of compounds 3, 8a, 8b, 13a and 13b were tested on human cancerous cells (HEPG2, PC-3, A-549, and DLD-1) as well as human healthy epithelium cell (PNT1A). Results show that compounds 3, 8a, 8b and 13b have cytotoxic potential on human colorectal carcinoma cells (DLD-1) with IC50 values of 43 µM, 45.2 µM, 64.57 µM, and 29.35 µM respectively. Apoptosis ratios of cell death were investigated with flow cytometer using 7-AAD and Annexin-V as markers. Cytotoxic potential of 8a was found to be higher due to increased apoptosis, when compared with healthy cells the apoptotic cell death was significantly (p < 0.0001) increased up to 1.7-fold and 2.4-fold in DLD-1 and A549 cells, respectively. In conclusion, these l-proline derived calix[4]arenes with their selective cytotoxic potential on human cancerous cells may be a potential candidate for the treatment of human CRC and lung cancer.

Inclusion of Quercetin in Gold Nanoparticles Decorated with Supramolecular Hosts Amplifies Its Tumor Targeting Properties.

Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential, we developed a nanohybrid delivery platform with a noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulfonatocalix[4]arene, enabling a 62 000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in an acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate noncovalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50-fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetin-loaded nanoparticles altered the expression of 27 genes related to apoptosis.

New water soluble Hg2+ selective fluorescent calix[4]arenes: Synthesis and application in living cells imaging.

The present study demonstrates the synthesis of water-soluble fluorescent calix[4]arenes (6 and 7) and its application in living cell imaging for Hg2+ detection at a low level. The synthesized fluorescent ligands 6 and 7 were characterized by 1H NMR technique. The fluorescent study showed both water soluble ligands were Hg2+ selective and follow photo-induced electron transfer (PET) process. From the fluorimeter titration experiment detection limit was calculated as 1.14×10-5 and 3.42×10-5 for ligand 6 and 7, respectively. From the Benesi-Hildebrand plot binding constant values were evaluated as 666.7 and 733.3M-1 for 6 and 7, respectively. The interactions between ligands 6 and 7 and Hg2+ were also demonstrated in living cells, SW-620, using Fluorescent Cell Imager. While ligands 6 and 7 alone show fluorescent properties, they loss their action with the presence of Hg2+ in SW-620 cells.

Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes.

The aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 µM and 29.1 µM, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p<0.0001). In addition, TA was found to have anti-invasive potential on PC-3 cells and it inhibited (80.9%, p<0.0001) invasion of PC-3 cells into matrigel. Only 17.8% of PC-3 cells can form colony in the 0.7% agarose after treatment of cells with TA at the IC50 value concentration. Furthermore, flow cytometry analyses with Annexin V-APC and 7-AAD staining demonstrated that TA increases early apoptosis rate of PC-3 cells by 25.8% and LNCaP cells by 20.9%. Besides, Western blot and qRT-PCR analyses also demonstrated that TA regulates protein and mRNA expressions of CYP17A1, CYP3A4, CYP2B6, NQO1, GSTM1 and GSTP1 enzymes. The results obtained from this study show that TA might be a good candidate for combinational therapy and highly effective strategic molecule for reducing the occurrence of PCa.

Contribution of ellagic acid on the antioxidant potential of medicinal plant Epilobium hirsutum.

In the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms,and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001).

Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer.

Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking therapies cause most of the deaths from prostate cancer, intensifying the need to fully understand CRPC pathophysiology. In this study, we characterized the transcriptomic differences between untreated prostate cancer and locally recurrent CRPC. Here, we report the identification of 145 previously unannotated intergenic long noncoding RNA transcripts (lncRNA) or isoforms that are associated with prostate cancer or CRPC. Of the one third of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in approximately 50% of human prostate cancer. Genome-wide expression analysis of a PCAT5-positive prostate cancer after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential, and apoptosis. Our findings reveal a key molecular determinant of differences between prostate cancer and CRPC at the level of the transcriptome. Furthermore, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions.