Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K/AKT inhibition.

In this study, seven isoniazid-hydrazone derivatives (3a-g) were synthesized and their structures elucidated by chromatographic techniques, and then the antiproliferative effects of these compounds on various cancer cells were tested. The advanced anticancer mechanism of the most potent compound was then investigated. Antiproliferative activities of the synthesized compounds were evaluated on human breast cancer MCF-7, lung cancer A-549, colon cancer HT-29, and non-cancerous mouse fibroblast 3T3-L1 cell lines by XTT assay. Flow cytometry analysis were carried out to determine cell cycle distribution, apoptosis, mitochondrial membrane potential, multi-caspase activity, and expression of PI3K/AKT signaling pathway. The XTT results showed that all the title molecules displayed cytotoxic activity at varying strengths in different dose ranges, and among them, the strongest cytotoxic effect and high selectivity were exerted by 3d against MCF-7 cells with the IC50 value of 11.35 µM and selectivity index of 8.65. Flow cytometry results revealed that compound 3d induced apoptosis through mitochondrial membrane disruption and multi-caspase activation in MCF-7 cells. It also inhibited the cell proliferation via inhibition of expression of PI3K/AKT and arrested the cell cycle at G0/G1 phase. In conclusion, all these data disclosed that among the synthesized compounds, 3d is notable for in vivo anticancer studies.

Diffractaic acid exerts anti-cancer effects on hepatocellular carcinoma HepG2 cells by inducing apoptosis and suppressing migration through targeting thioredoxin reductase 1.

Hepatocellular carcinoma (HCC) represents one of the most common malignant tumors worldwide. Due to the limited number of available drugs and their side effects, the development of new chemotherapeutic strategies for HCC treatment has become increasingly important. This study is aimed at investigating whether diffractaic acid (DA), one of the secondary metabolites of lichen, exhibits a potential anticancer effect on HepG2 cells and whether its anticancer effect is mediated by inhibition of thioredoxin reductase 1 (TRXR1), which is a target of chemotherapeutic strategies due to overexpression in tumor cells including HCC. XTT assay results showed that DA exhibited strong cytotoxicity on HepG2 cells with an IC50 value of 78.07 µg/mL at 48 h. Flow cytometric analysis results revealed that DA displayed late apoptotic and necrotic effects on HepG2 cells. Consistent with these findings, real-time PCR results showed that DA did not alter the BAX/BCL2 ratio in HepG2 cells but upregulated the P53 gene. Moreover, the wound healing assay results revealed a strong anti-migratory effect of DA in HepG2 cells. Real-time PCR and Western blot analyses demonstrated that DA increased TRXR1 gene and protein expression levels, whereas enzyme activity studies disclosed that DA inhibited TRXR1. These findings suggest that DA has an anticancer effect on HepG2 cells by targeting the enzymatic inhibition of TRXR1. In conclusion, DA as a TRXR1 inhibitor can be considered an effective chemotherapeutic agent which may be a useful lead compound for the treatment of HCC.

Chalcone-based imidazo[2,1-b]thiazole derivatives: synthesis, crystal structure, potent anticancer activity, and computational studies.

In this work, two novel chalcone-based imidazothiazole derivatives ITC-1 and ITC-2 were synthesized and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry with electrospray ionization, and chemical structure of ITC-1 was confirmed by single-crystal X-ray diffraction. Also, the anticancer activity of ITC-1 and ITC-2 was evaluated. First, antiproliferative activity tests were performed against cancer cells namely, human-derived breast adenocarcinoma (MCF-7), lung carcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast healthy cell line (3T3-L1) by XTT assay. Afterward, mitochondrial membrane disruption (MMP), caspase activity, and apoptosis tests were performed on MCF-7 cells to elucidate the anticancer mechanism of action of the test compounds by flow cytometry analysis. XTT results revealed that both compounds exhibited a very high degree of antiproliferative effects on each tested cancer cell line with very low IC50 values while showing much lower antiproliferation on 3T3-L1 normal cells with much higher IC50 values. Besides, ITC-2 was determined to have a striking cytotoxic power competing with the chemotherapeutic drug carboplatin. Flow cytometry results demonstrated the mitochondrial-mediated apoptotic effects of both compounds through membrane disruption and multi-caspase activation in MCF-7 cells. Finally, molecular docking studies were performed to determine the structural understanding of the test compounds by their interactions on caspase-3 and DNA dodecamer enzymes, respectively. The interactions between the compound and the crystal structure were determined according to parameters such as free binding energies (ΔGBind), Glide score values, and determination of the active binding site. The obtained data suggest that ITC-1 and ITC-2 may be considered remarkable anticancer drug candidates. In addition to molecular docking via in silico approaches, the pharmacokinetic properties of compounds ITC-1 and ITC-2 were calculated using the Schrödinger 2021-2 Qikprop wizard.Communicated by Ramaswamy H. Sarma.

Novel Pyrazole-Based Benzofuran Derivatives as Anticancer Agents: Synthesis, Biological Evaluation, and Molecular Docking Investigations.

In this work, the design, synthesis, and mechanistic studies of novel pyrazole-based benzofuran derivatives 1-8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A-549, human-derived colorectal adenocarcinoma HT-29, breast adenocarcinoma MCF-7 cells as well as mouse fibroblast 3T3-L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose-dependent anti-proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti-proliferative activity with an IC50 value of 7.31 µM and the highest selectivity (15.74) on MCF-7 cells. Flow cytometry results confirmed that the cytotoxic power of compound 2 on MCF-7 cells is closely related to mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase-3 via in-silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.

Diffractaic acid exhibits thioredoxin reductase 1 inhibition in lung cancer A549 cells.

Lung cancer is the leading cause of cancer-related deaths all over the world. Therefore, it has gained importance in the development of new chemotherapeutic strategies to identify anticancer agents with low side effects, reliable, high anticancer potential, and specific to lung cancer cells. Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for lung cancer treatment because of its overexpression in tumor cells. Here, we aimed to examine the anticancer effect of diffractaic acid, a lichen secondary metabolite, in A549 cells by comparing it with the commercial chemotherapeutic drug carboplatin and also to investigate whether the anticancer effect of diffractaic acid occurs via TrxR1-targeting. The IC50 value of diffractaic acid on A549 cells was determined as 46.37 µg/mL at 48 h, and diffractaic acid had stronger cytotoxicity than carboplatin in A549 cells. qPCR results revealed that diffractaic acid promoted the intrinsic apoptotic pathway through the upregulation of the BAX/BCL2 ratio and P53 gene in A549 cells, which is consistent with the flow cytometry results. Furthermore, migration analysis results indicated that diffractaic acid impressively suppressed the migration of A549 cells. While the enzymatic activity of TrxR1 was inhibited by diffractaic acid in A549 cells, no changes were seen in the quantitative expression levels of gene and protein. These findings provide fundamental data on the anticancer effect of diffractaic acid on A549 cells targeting TrxR1 activity, suggesting that it could be considered a chemotherapeutic agent for lung cancer therapy.

Effect of evernic acid on human breast cancer MCF-7 and MDA-MB-453 cell lines via thioredoxin reductase 1: A molecular approach.

Thioredoxin reductase 1 (TrxR1) has emerged as an important target for anticancer drug development due to its overexpression in many human tumors including breast cancer. Due to the serious side effects of currently used commercial anticancer drugs, new natural compounds with very few side effects and high efficacy are of great importance in cancer treatment. Lichen secondary metabolites, known as natural compounds, have diverse biological properties, including antioxidant and anticancer activities. Herein, we aimed to determine the potential antiproliferative, antimigratory, and apoptotic effects of evernic acid, a lichen secondary metabolite, on breast cancer MCF-7 and MDA-MB-453 cell lines and afterward to investigate whether its anticancer effect is exerted by TrxR1-targeting. The cytotoxicity results indicated that evernic acid suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose-dependent manner and the IC50 values were calculated as 33.79 and 121.40 µg/mL, respectively. Migration assay results revealed the notable antimigratory ability of evernic acid against both cell types. The expression of apoptotic markers Bcl2 associated X, apoptosis regulator, Bcl2 apoptosis regulator, and tumor protein p53 by quantitative real-time polymerase chain reaction and western blot analysis showed that evernic acid did not induce apoptosis in both cell lines, consistent with flow cytometry results. Evernic acid showed its anticancer effect via inhibiting TrxR1 enzyme activity rather than mRNA and protein expression levels in both cell lines. In conclusion, these findings suggest that evernic acid has the potential to be evaluated as a therapeutic agent in breast cancer treatment.

Isolation, characterization and anticancer activity of secondary metabolites from Verbascum speciosum.

Herein, two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-TOF/MS). Antiproliferative activities of Aucubun (1) and Verbascoside (3) were tested against A-549 (human colon cancer), MDA-MD-453 (human breast cancer) and 3T3-L1 (mouse fibroblast)cell lines by XTT assay. In addition, the anticarcer mechanism of action of aucubin (1) was investigated on MDA-MB-453 cells for the first time. XTT result showed that both applied compounds exhibited antiproliferative effect at different dose ranges depending on the cancer type, as well as selectivity between cancer and healty cell lines. Flow cytometry analyzes revealed that aucubin (1) exerts its cytotoxic effect in MDA-MB-453 cells by directing cells to early apoptosis and inhibiting the P13K/AKT signaling pathway.

Isolation and cytotoxic activities of undescribed iridoid and xanthone glycosides from Centaurium erythraea Rafn. (Gentianaceae).

Centaurium erythraea Rafn. (Gentianaceae) is used in internal traditional therapy as an anthelmintic, hypotensive, antipyretic, and antidiabetic. It is used externally for the treatment of wounds. Ursolic acid, maslinic acid, secologanin, secologanin dimethyl acetal, centauroside A, erythraeaxanthone I, erythraeaxanthone II, and demethyleustomin were isolated from aerial parts of Centaurium erythraea and were identified using spectroscopic methods, including NMR and mass spectrometry. The cytotoxic potency of undescribed compounds was evaluated by the XTT assay against human breast cancer MCF-7, MDA-MB-453 and mouse fibroblast 3T3-L1 cell lines. Erythraeaxanthone II was found to have the most potent cytotoxic activity.

Inhibition of thioredoxin reductase 1 by vulpinic acid suppresses the proliferation and migration of human breast carcinoma.

AIMS: It was aimed to investigate the thioredoxin reductase 1 (TrxR1)-targeted anticancer effect of vulpinic (VA) and lecanoric (LA) acids, which are lichen secondary metabolites, on breast cancer MCF-7 and MDA-MB-453 cell lines, and to compare the effectiveness of this potential effect against commercial chemotherapeutic drugs carboplatin and docetaxel. MAIN METHODS: The anticancer effects of both lichen metabolites were evaluated by XTT, flow cytometry analysis, cell scratch, and transwell migration assays. Apoptotic results were also confirmed by qPCR and western blot. Changes in TrxR1 were investigated in gene and protein expressions and enzyme activity levels. KEY FINDINGS: VA suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose- and time-dependent manner, and the IC50 values were calculated as 22.92 µg/ml and 95.65 µg/ml, respectively. As for LA, it did not have a considerable antiproliferative effect on both cell lines. VA had stronger cytotoxicity than both chemotherapeutic drug in MCF-7 cells and showed antiproliferative activity closer to carboplatin in MDA-MB-453 cells. qPCR, western blot, and flow cytometry analysis results revealed that VA did not induce apoptosis in both cell lines. In contrast, VA caused cell cycle arrest, significantly. Migration assay results showed that VA suppressed migration in both cells. VA induced the gene expression of TrxR1 while inhibiting its protein expression and enzymatic activity in both cell lines. SIGNIFICANCE: The findings reveal that vulpinic acid may be a novel inhibitor candidate on TrxR1 and could be considered a potential chemotherapeutic agent for breast cancer treatment, especially in MCF-7 cells.

Fluorescence interactions of a novel chalcone derivative with membrane model systems and human serum albumin.

A novel chalcone derivative (4-(5-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (PDP) was synthesized, characterized and investigated for its potential as a fluorescent probe. The structure of the synthesized molecule was determined by FTIR, 1H NMR, 13C NMR and LC-MS/MS. The interactions of PDP with fluorescent dyes in aqueous SDS environment and HSA were studied by using fluorescence resonance energy transfer (FRET) technique and steady-state and time-resolved fluorescence spectroscopy techniques. In addition, the cytotoxic effects of PDP against various cell lines (MCF -7, HT -29, and 3 T3-L1) as well as their corresponding healthy cell lines were tested by MTT assay and visualization of FRET efficiency of PDP in vitro was monitored by confocal microscopy. MTT assay showed that PDP has no significant cytotoxic effect on HT -29 cancer cells and moderate cytotoxicity on MCF -7 and 3 T3-L1 cells even at a concentration of 250 µM. Combining confocal microscopes with the FRET technique showed that PDP significantly stained the cytoplasm of MCF -7 cell lines. These results suggest that PDP could be used in fluorescence microscopy for cell staining.

A Biochemical Approach for Hedysarum candidissimum from Turkey: Screening Phytochemicals, Evaluation of Biological Activites, and Molecular Docking Study.

This study was designed to screen the phytochemical composition and investigate the biological activities of Hedysarum candidissimum extracts and also support the results with molecular docking studies. LC/MS/MS analysis revealed the presence of 22 phytochemical constituents (mainly phenolic acids, flavonoids, and flavonoid glycosides) in the plant structure. The methanol extract exhibited the strongest antioxidant activity among all the extracts with its strong DPPH radical scavenging and iron reducing capacity, as well as high phenolic and flavonoid contents. Additionally, it was found to be the most promising acetylcholinesterase (AChE: IC50 : 93.26 µg/mL) and α-glycosidase (AG: IC50 : 28.57 µg/mL) inhibitory activities, supported by the major phenolics of the species through in silico studies. Ethyl acetate extract had the strongest cytotoxic effect on HT-29 (IC50 : 63.03 µg/mL) and MDA-MB-453 (IC50 : 95.36 µg/mL) cancer cell lines. Both extracts exhibited considerable apoptotic and anti-migrative effects on HT-29 cells. The investigations provide phyto-analytical and bio-pharmacological results which can be extended by in vivo studies in the future.

Diffractaic acid, a novel TrxR1 inhibitor, induces cytotoxicity, apoptosis, and antimigration in human breast cancer cells.

Breast cancer represents one of the most frequently encountered cancer types among women worldwide. Thioredoxin reductase 1 (TrxR1) is a therapeutic target for breast cancer therapy due to its overexpression in tumor cells. The current research aims to determine the anticancer effect of diffractaic acid, a lichen acid, in breast cancer, and research whether the anticancer effect of diffractaic acid occurs through TrxR1 targeting. According to the XTT assay results, diffractaic acid induced cytotoxicity in both MCF-7 and MDA-MB-453 cells with IC50 values of 51.32 µg/ml and 87.03 µg/ml, respectively. Flow cytometry and cell migration analyses revealed the apoptotic, necrotic, and antimigratory effects of diffractaic acid. qPCR analysis indicated the upregulation of the BAX/BCL2 ratio and the P53 gene in MCF-7 cells with only the P53 gene in MDA-MB-453 cells. The gene, protein, and enzyme activity of TrxR1 were suppressed in MCF-7 cells, whereas only enzyme activity was suppressed in MDA-MB-453 cells. These findings illustrate the anticancer effect of diffractaic acid on breast cancer targeting TrxR1. In conclusion, these data reveal that diffractaic acid may be considered an effective therapeutic agent for breast cancer treatment.

Silver(I) complexes containing diclofenac and niflumic acid induce apoptosis in human-derived cancer cell lines.

We investigated the anti-cancer activity of [Ag(µ-dicl)]n 1 and [AgH(nif)2] 2 complexes against human cancer cell lines (MCF-7, HT-29, and HepG2) and mouse fibroblast (3T3-L1) cell line. Anti-proliferative activity was monitored by XTT cell viability and LDH leakage assays. Cell death mode was evaluated by multi-caspase activity, annexin V cytofluorimetric, MMP, cell cycle arrest, and ROS generation assays. Antioxidant capacity was evaluated on SOD, GPx, GR, and CAT enzymes. The XTT and LDH assay results showed that both complexes exhibited strong cytotoxicity against the tested cancer cell lines. The apoptotic mechanisms of the complexes were demonstrated by loss of MMP and increase in phosphatidylserine translocation, sub-G1 phase, and multi-caspase activity. Besides, both complexes induced the oxidative stress in MCF-7 cells by decreasing the activity of GPx, GR, and CAT enzymes. In conclusion, both Ag(I) complexes, especially 1, warrant for further in vivo evaluation as a new alternative in cancer treatment.HighlightsAg(I) complexes inhibited cell proliferation and induced LDH leakage in human cancer cell lines.Ag(I) complexes induced apoptosis through MMP disruption and ROS generation.Ag(I) complexes mimicked the multi-caspase activity.Ag(I) complexes increased the accumulation of sub-G1 phase.Ag(I) complexes inhibited the activity of antioxidant system enzymes.

In Vitro Anticancer Activity of Novel Co(II) and Ni(II) Complexes of Non-steroidal Anti-inflammatory Drug Niflumic Acid Against Human Breast Adenocarcinoma MCF-7 Cells.

Herein, we report the synthesis, characterization and anticancer activity of six novel complexes of non-steroidal anti-inflammatory drug niflumic acid with Co(II) and Ni(II). In vitro cytotoxicity screening in MCF-7, HepG2 and HT-29 cancer cell lines showed that the complex 3 [Co(nif)2(met)(4-pic)] and complex 6 [Ni(nif)2(met)(4-pic)] among all the complexes exhibited the highest cytotoxicity against MCF-7 cells with IC50 values of 11.14 µM and, 41.47 µM, respectively. Besides, all the complexes exhibited significantly higher selectivity towards mouse fibroblast 3T3L1 cells. Further mechanistic studies with both complexes on MCF-7 cells revealed their cytotoxic action through the mitochondrial-dependent apoptotic pathway causing an increase oxidative/nitrosative stress, decrease in mitochondrial membrane potential (ΔΨm), inducing the multicaspase activation and arresting the cell cycle at S phase. q-PCR analysis resulted in an increase in the expression of the apoptotic marker proteins bax, p53 and caspase-3 and -8 in MCF-7 cells, but a decrease in the expression of antiapoptotic bcl-2 gene. Moreover, both complexes induced the apoptosis through the inhibition of PI3K/Akt signaling pathway by decreasing the expression of PI3K and increasing dephosphorylation form of Akt protein. These results provide a significant contribution to the explanation of the anticancer mechanisms of these complexes in MCF-7 cells.

In†vitro Antioxidant and Cytotoxic Activities of Extracts of Endemic Tanacetum erzincanense Together with Phenolic Content by LC-ESI-QTOF-MS.

In this study, phenolic composition, and in vitro biological activities of ethyl acetate (EAE) and methanol (ME) extracts obtained from the aerial parts of endemic Tanacetum erzincanense were investigated. Total phenolic and flavonoid content of the extracts were determined by Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Antioxidant capacity of the extracts was evaluated over radical scavenging (DPPH and ABTS) and metal ion reducing power (FRAP and CUPRAC) tests. Individual phenolic compounds in ME was analyzed by high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF/MS). Cell inhibitory potential of the extracts was tested against colorectal adenocarcinoma (HT-29), breast adenocarcinoma (MCF-7), and hepatocarcinoma (HepG2) cells by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The results showed that ME contains higher TPC (64.4 mg GAE/g) and TFC (62.2 mg QE/g) than those of EAE (41.5 mg GAE/g and 40.0 mg QE/g). LC-ESI-QTOF/MS analysis revealed that ME is rich in phenolic compounds, namely, chlorogenic acid, apigenin, quercetin, luteolin, and diosmetin. Antioxidant assay results indicated that ME possess stronger activity than EAE and a power that competes with synthetic antioxidants. XTT assay results demonstrated that although both extracts displayed a considerable cytotoxicity against the tested cancer cell lines in a time and dose-dependent manner, ME expressed its selective inhibitory action towards MCF-7 cells with an IC50 value of 20.4 µg/mL for 72 h. These results may serve as a basis for further in vivo studies to examine the potential applications of T. erzincanense in food and pharmaceutical industries.

Preliminary phytochemical analysis and evaluation of in vitro antioxidant, antiproliferative, antidiabetic, and anticholinergics effects of endemic Gypsophila taxa from Turkey.

The phenolic contents and antioxidant, anticancer, antidiabetic, and anticholinergic potentials of four endemic Gysophila taxa (G. pallida, G. arrosti, G. tuberculosa, and G. eriocalyx) were investigated. The HPLC analysis showed that methanol extracts of all the tested species were richer in phenolics than water extracts. 3,4-dihydroxybenzoic acid, p-hydroxybenzoic acid, vanillin, syringic acid, and p-coumaric acid were detected in all extracts. In parallel to the phenolic contents, methanol extracts displayed comparatively higher antioxidant activity than water extracts. Additionally, all extracts exhibited dose-dependent antiproliferative activity on the cancer cell lines with lower IC50 values changing from 0.170 to 1.805 mg/ml. Moreover, the extracts impressively inhibited the acetylcholinesterase (0.63-26.04), butyrylcholinesterase (3.66-10.73), and α-glycosidase (98.52-235.55) enzymes with very low IC50 (mg/ml) values. Together, the present results indicate that Gysophila taxa have various biological activities together with higher phenolic contents. Hence, these species hold good potential for use in the pharmaceutical industry. PRACTICAL APPLICATIONS: Gypsophila taxa having numerous biological activities have been used for different purpose in folk medicine as well as their use in the food industry. The obtained results of the current study indicated that the extracts of Gypsophila taxa are rich in phenolics and flavonoids with powerful antioxidant and antiproliferative activity against different type of cancer cell lines. In addition, the extracts obtained from these taxa showed notable antidiabetic and anticholinergics effects. Gypsophila taxa could be used as a natural material to develop anticancer, antidiabetic, and anticholinergic drugs.

Salvia fruticosa Modulates mRNA Expressions and Activity Levels of Xenobiotic Metabolizing CYP1A2, CYP2E1, NQO1, GPx, and GST Enzymes in Human Colorectal Adenocarcinoma HT-29 Cells.

Natural products have gained considerable interests because of their use in some industrial areas including nutrition, cosmetic, pharmacy, and medicine. Salvia fruticosa M. (Lamiaceae) is known for its antioxidant, antimicrobial, and antiproliferative activities. Phase I xenobiotic metabolizing enzymes, CYP1A2 and CYP2E1, produce reactive metabolites which are eliminated by the action of phase II enzymes, NQO1, GPx, and glutathione S-transferases (GSTs). In this study, in vitro modulatory effects of S. fruticosa and its major phenolic compound rosmarinic acid (RA) on CYP1A2, CYP2E1, NQO1, GPx, and GSTm1 mRNA expressions and enzyme activities of GPx and GSTs were investigated in HT-29 cells. An mRNA expression analysis revealed that CYP1A2 and CYP2E1 levels were decreased while those of NQO1, GPx, and GSTm1 increased after S. fruticosa and RA treatments. In parallel to gene expressions, enzyme activities of GPx and GSTs by S. fruticosa increased 1.68- and 1.48-fold, respectively. Moreover, RA increased GPx and GSTs activities 1.67- and 1.94-fold, respectively. The results of this preliminary study show that metabolism of xenobiotics may be altered due to changes in the expression and activity of the investigated enzymes by S. fruticosa.

Glassworts as Possible Anticancer Agents Against Human Colorectal Adenocarcinoma Cells with Their Nutritive, Antioxidant and Phytochemical Profiles.

In this study, the possible uses of glassworts as potential food ingredients and their antiproliferative activity against colorectal adenocarcinoma cells together with their antioxidant and phytochemical profiles were investigated for the first time. MeOH extracts of five different taxa collected from different localities were screened for their antioxidant capacities by DPPH (IC50 2.91 - 5.49 mg/ml) and ABTS (24.4 - 38.5 µmol TE/g extract) assays. Salicornia freitagii exhibited the highest DPPH radical scavenging activity. LC/MS/MS analysis displayed that vanillic acid and p-coumaric acid were two main phenolic compounds in the extract. Salicornia freitagii extracts also exhibited high antiproliferative activity against HT-29 (IC50 1.67 mg/ml) and Caco-2 (IC50 3.03 mg/ml) cells for 72 h. Mineral analysis indicated that all the species with different proportions of elemental components contained high amount of cations. These results indicate that investigated glassworts, with their high phenolic and mineral contents and also notable antioxidant and cytotoxic properties, may be utilized as a promising source of therapeutics.

Wild Edible Mushrooms from Turkey as Possible Anticancer Agents on HepG2 Cells Together with Their Antioxidant and Antimicrobial Properties.

This study was designed to reveal cell growth inhibitory potential of six different edible mushrooms: Ramaria flava, Agrocybe molesta, Volvopluteus gloiocephalus, Lactarius deliciosus, Bovista plumbea, and Tricholoma terreum on HepG2 cells together with their antioxidant and antibacterial power. Methanolic extracts of V gloiocephalus and aqueous extracts of R. flava had the most potential cytotoxic effects over HepG2 cells. The best results for 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities were obtained from both aqueous and methanolic extracts of R. flava. Methanolic extracts of T. terreum (IC50 = 1.62 mg/mL) and aqueous extracts of B. plumbea (IC50 = 0.49 mg/mL) showed maximum metal chelating activity. The highest reducing capacities were observed among the methanolic extracts of R. flava (EC50 = 1.65 mg/mL) and aqueous extracts of B. plumbea (EC50 = 1.71 mg/ mL). High-performance liquid chromatography analysis revealed the presence of many phenolic compounds in macrofungi; gallic acid and p-coumaric acid were the two main phenolics identified in all extracts. Antibacterial studies indicated that all six tested mushrooms showed antibacterial activity on at least three microorganisms. These results indicate that different extracts of the investigated mushrooms have considerable cytotoxic, antioxidant, and antibacterial properties and may be utilized as a promising source of therapeutics.

The relationship between lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction: the role of autonomic hyperactivity.

BACKGROUND/AIM: To investigate whether autonomic nervous system (ANS) hyperactivity may be a potential cause for the relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). MATERIALS AND METHODS: Twenty-four patients were recruited for this study. Complete physical examinations, urine analysis, uroflowmetry, and postvoid residual urine volume (PVRU) analysis were performed. The potential impact of some factors such as hyperglycemia, obesity, and hyperlipidemia were analyzed. These values were correlated with the various symptom scores. We performed an electromyographic and an electrocardiographic evaluation. The alterations after treatment with 2 different alpha-blockers were also analyzed. RESULTS: The electromyographic and electrocardiographic assessments revealed a minimal increase in ANS activity and it did not change significantly after treatment (P > 0.05). After treatment, maximum flow rate increased and PVRU decreased significantly (P < 0.001 and P < 0.001, respectively); total and free testosterone levels increased significantly (P = 0.0068 and P = 0.0071, respectively). There was a statistically significant difference between the 2 treatment groups regarding the outcomes of the Danish Prostate Symptom Score questionnaire (P = 0.047). CONCLUSION: This current study suggested that the effect of ANS hyperactivity is not the fundamental factor underlying the relationship between LUTS and ED.