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In this study, Schiff base substituted phthalocyanine complexes (Zn1c, Zn2c) and their quaternized derivatives (Q-Zn1c, Q-Zn2c) were synthesized for the first time. Their structures have been characterized by FT-IR, 1H-NMR, UV–Vis, mass spectrometry and elemental analysis as well as. The photophysicochemical properties (fluorescence, singlet oxygen and photodegradation quantum yield) of these novel complexes were investigated in dimethylsulfoxide (DMSO) for both non-ionic and quaternized cationic phthalocyanine complexes and in aqueous solution for quaternized cationic phthalocyanine complexes. Water soluble cationic phthalocyanine compounds gave good singlet oxygen quantum yield (0.65 for Q-Zn1c, 0.66 for Q-Zn2c in DMSO; 0.65 for Q-Zn2c in aqueous solution). The binding of Q-Zn1c and Q-Zn2c to BSA/DNA was studied by using UV–Vis and fluorescence spectroscopy and these. Studies indicate that the mechanism of BSA quenching by quaternized zinc(II) phthalocyanines was static quenching. Quaternized zinc(II) phthalocyanines interacted with ct-DNA by intercalation. Quaternized zinc(II) phthalocyanines caused a decrease in cell viability and triggered apoptotic cell death after PDT was applied at a concentration that did not have a toxic effect on their own. Q-Zn1c and Q-Zn2c mediated PDT reduced the activity of SOD, CAT, GSH while increased MDA level in the prostate cancer cells. Furthermore, expression of apoptotic proteins after PDT was examined. The results revealed that the synthesized water soluble quaternized zinc(II) phthalocyanine complexes (Q-Zn1c and Q-Zn2c) are promising potential photosensitizers for PDT. [ABSTRACT FROM AUTHOR]

A series of novel fluorinated 1,5-benzothiazepine derivatives were synthesized, characterized and evaluated for in vitro anticancer and antibacterial activity. The in vitro anticancer activity of the synthesized compounds 4a–h was evaluated against four human cancer cell lines namely lung (A549), breast (MCF-7), liver (HEPG2) and prostate (PC-3). Compounds 4c, 4d, 4g and 4h exhibited good activity with GI50

Fluoro-substituted zinc(II)phthalocyanines (RS)4ZnPcs were prepared. All the structures of newly synthesized compounds was evaluated by IR and ¹H NMR spectral analysis. They were tested against human adenocarcinoma prostate cancer cells. A type II membrane antigen highly expressed in prostate cancer, namely prostate-specific membrane antigen, has been an attractive target for imaging and therapy. To investigate the structureactivity relationships of (RS)4ZnPcs 4a-c in human adenocarcinoma prostate cancer cell model, 3 fluoro-substituted zinc(II)phthalocyanines with different terminal heteroaromatic rings have been designed and evaluated for their antiproliferative potency in vitro. The detailed LD50 values of the targeted compounds were reported. Our preliminary in vitro studies confirm that (RS)4ZnPcs 4a-c could act as an attractive photosensitizer for the early diagnosis of prostate cancer. [ABSTRACT FROM AUTHOR]

One of the greatest bottlenecks in extracellular vesicle (EV) research is the production of sufficient material in a consistent and effective way using in vitro cell models. Although the production of EVs in bioreactors maximizes EV yield in comparison to conventional cell cultures, the impact of their cell growth conditions on EVs has not yet been established. In this study, we grew two prostate cancer cell lines, PC-3 and VCaP, in conventional cell culture dishes and in two-chamber bioreactors to elucidate how the growth environment affects the EV characteristics. Specifically, we wanted to investigate the growth condition-dependent differences by non-targeted metabolite profiling using liquid chromatography–mass spectrometry (LC–MS) analysis. EVs were also characterized by their morphology, size distribution, and EV protein marker expression, and the EV yields were quantified by NTA. The use of bioreactor increased the EV yield >100 times compared to the conventional cell culture system. Regarding morphology, size distribution and surface markers, only minor differences were observed between the bioreactor-derived EVs (BR-EVs) and the EVs obtained from cells grown in conventional cell cultures (C-EVs). In contrast, metabolomic analysis revealed statistically significant differences in both polar and non-polar metabolites when the BR-EVs were compared to the C-EVs. The results show that the growth conditions markedly affected the EV metabolite profiles and that metabolomics was a sensitive tool to study molecular differences of EVs. We conclude that the cell culture conditions of EV production should be standardized and carefully detailed in publications and care should be taken when EVs from different production platforms are compared with each other for systemic effects.

One of the greatest bottlenecks in extracellular vesicle (EV) research is the production of sufficient material in a consistent and effective way using in vitro cell models. Although the production of EVs in bioreactors maximizes EV yield in comparison to conventional cell cultures, the impact of their cell growth conditions on EVs has not yet been established. In this study, we grew two prostate cancer cell lines, PC-3 and VCaP, in conventional cell culture dishes and in two-chamber bioreactors to elucidate how the growth environment affects the EV characteristics. Specifically, we wanted to investigate the growth condition-dependent differences by non-targeted metabolite profiling using liquid chromatography–mass spectrometry (LC–MS) analysis. EVs were also characterized by their morphology, size distribution, and EV protein marker expression, and the EV yields were quantified by NTA. The use of bioreactor increased the EV yield >100 times compared to the conventional cell culture system. Regarding morphology, size distribution and surface markers, only minor differences were observed between the bioreactor-derived EVs (BR-EVs) and the EVs obtained from cells grown in conventional cell cultures (C-EVs). In contrast, metabolomic analysis revealed statistically significant differences in both polar and non-polar metabolites when the BR-EVs were compared to the C-EVs. The results show that the growth conditions markedly affected the EV metabolite profiles and that metabolomics was a sensitive tool to study molecular differences of EVs. We conclude that the cell culture conditions of EV production should be standardized and carefully detailed in publications and care should be taken when EVs from different production platforms are compared with each other for systemic effects. [ABSTRACT FROM AUTHOR]

High-throughput transcriptomic (HTTr) technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. Here, we describe the development and validation of a novel gene expression biomarker to identify androgen receptor (AR)-modulating chemicals using a pattern matching method. Androgen receptor biomarker genes were identified by their consistent expression after exposure to 4 AR agonists and 4 AR antagonists and included only those genes that were regulated by AR. The 51 gene biomarker was evaluated as a predictive tool using the fold-change, rank-based Running Fisher algorithm. Using 158 comparisons from cells treated with 95 chemicals, the biomarker gave balanced accuracies for prediction of AR activation or AR suppression of 97% or 98%, respectively. The biomarker correctly classified 16 out of the 17 AR reference antagonists including those that are "weak" and "very weak". Predictions based on microarray profiles from AR-positive LAPC-4 cells treated with 28 chemicals in antagonist mode were compared with those from an AR pathway model which used 11 in vitro HT assays. The balanced accuracy for suppression was 93%. Using our approach, we identified conditions in which AR was modulated in a large collection of microarray profiles from prostate cancer cell lines including (1) constitutively active mutants or knockdown of AR, (2) decreases in availability of androgens by castration or removal from media, and (3) exposure to chemical modulators that work through indirect mechanisms including suppression of AR expression. These results demonstrate that the AR gene expression biomarker could be a useful tool in HTTr to identify AR modulators. [ABSTRACT FROM AUTHOR]

Dactylolide and certain analogues are attractive targets for study due to their structural resemblance to zampanolide, a very promising anticancer lead compound and a unique covalent-binding microtubule stabilizing agent. The primary goal of this project is identification and synthesis of simplified analogues of dactylolide that would be easier to prepare and could be investigated for antiproliferative activity in comparison with zampanolide. Extension of Almann’s concept of a simplified zampanolide analogue to dactylolide in the form of desTHPdactylolide was attractive not only for reasons of synthetic simplification but also for the prospect that analogues of dactylolide could be prepared in both (17 S ) and (17 R ) configurations. Since Altmann’s overall yield for the six-step procedure leading to the C9–C18 fragment of desTHPdactylolide was only 8.7%, a study focused on optimized synthesis and antiproliferative evaluation of each enantiomer of desTHPdactylolide was initiated using Altmann’s route as a framework. To this end, two optimized approaches to this fragment C9–C18 were successfully developed by us using allyl iodide or allyl tosylate as the starting material for a critical Williamson ether synthesis. Both (17 S ) and (17 R ) desTHPdactylolides were readily synthesized in our laboratory using optimized methods in yields of 37–43%. Antiproliferative activity of the pair of enantiomeric desTHPdactylolides, together with their analogues, was evaluated in three docetaxel-sensitive and two docetaxel-resistant prostate cancer cell models using a WST-1 cell proliferation assay. Surprisingly, (17 R ) desTHPdactylolide was identified as the eutomer in the prostate cancer cell models. It was found that (17 S ) and (17 R ) desTHPdactylolide exhibit equivalent antiproliferative potency towards both docetaxel-sensitive (PC-3 and DU145) and docetaxel-resistant prostate cancer cell lines (PC-3/DTX and DU145/DTX). [ABSTRACT FROM AUTHOR]

BackgroundCurcumin (diferuloylmethane) is a polyphenol derived from the plantCurcuma longa, commonly called turmeric. Extensive research over the last 50 years has demonstrated that these polyphenols play an important role in the maintenance of health and prevention of diseases, in addition to its therapeutic benefits such as anti-tumor, anti-inflammatory, and anti-oxidant activities.Materials and methodsThis study is devoted to the enhancement of the solubility and bioavailability of curcumin nanoparticles prepared by a process based on a wet-milling technique and then examinein vitroagainst prostate cancer cell line 3 (PC3), human embryonic kidney cell line (HEK), human erythrocytes (red blood cells (RBCs)), and against fourth different bacterial strains two gram-positive (Micrococcus luteus ATCC 9341,Staphylococcus aureus ATCC 29213), two gram-negative (Escherichia coli ATCC 25922,Pseudomonas aeruginosa ATCC 27853).ResultsThe cell viability curve, the half maximal inhibitory concentration (IC50), and the minimum bactericidal concentration (MBC) were evaluated. Nanocurcumin displayed significant activity against cancer cell line (PC3) and low toxicity against normal cells (HEK) compared with parent curcumin in favor of PC3 (P < 0.05). In addition, it was found that the efficiency of toxicity for nanocurcumin against PC3 (E% = 59.66%) was much better than HEK (E% = 36.07%) compared with parent curcumin. The results also demonstrate that, although nanocurcumin has a little more ability to lays RBCs than parent curcumin after incubated 60 min, but the hemolysis % remained very low and there was no significant difference between hemolysis % of nanocurcumin and parent curcumin (P > 0.05). On the other hand, the results demonstrate that, the MBCs of nanocurcumin were lower than curcumin for all different bacterial strains. Moreover, the selected gram-positive bacteria had higher sensitivity than the selected gram-negative bacteria for both curcumin and nanocurcumin. In conclusion, all these findings not only indicate that nanocurcumin safe compound has a potent ability as anti-cancer and antimicrobial activities, but also well justify the avail of using nanocurcumin as prostate cells PC3 anti-cancer, and antimicrobial agent for nanocurcumin are markedly improved by decreasing particle size to the nano-scale regime. [ABSTRACT FROM AUTHOR]

In the present work, different biopolymer blend scaffolds based on the silk protein fibroin from Bombyx mori (BM) were prepared via freeze-drying method. The chemical, structural, and mechanical properties of the three dimensional (3D) porous silk fibroin (SF) composite scaffolds of gelatin, collagen, and chitosan as well as SF from Antheraea pernyi (AP) and the recombinant spider silk protein spidroin (SSP1) have been systematically investigated, followed by cell culture experiments with epithelial prostate cancer cells (LNCaP) up to 14 days. Compared to the pure SF scaffold of BM, the blend scaffolds differ in porous morphology, elasticity, swelling behavior, and biochemical composition. The new composite scaffold with SSP1 showed an increased swelling degree and soft tissue like elastic properties. Whereas, in vitro cultivation of LNCaP cells demonstrated an increased growth behavior and spheroid formation within chitosan blended scaffolds based on its remarkable porosity, which supports nutrient supply matrix. Results of this study suggest that silk fibroin matrices are sufficient and certain SF composite scaffolds even improve 3D cell cultivation for prostate cancer research compared to matrices based on pure biomaterials or synthetic polymers. [ABSTRACT FROM AUTHOR]

• Prostate cancer cells show different radiosensitivity than reference cells. • Radiosensitivity differences affect the final clinical dose distribution. • Prostate cancer cell-based clinical dose from one-directional irradiation is no longer flat. • Opposed left–right irradiation used in clinic improves this lack of flatness. [Purpose] Treatment plans for carbon ion radiotherapy (CIRT) in Japan are designed to uniformly deliver the prescribed clinical dose based on the radiosensitivity of human salivary gland (HSG) cells to the planning target volume (PTV). However, sensitivity to carbon beams varies between cell lines, that is, it should be checked that the clinical dose distribution based on the cell radiosensitivity of the treatment site is uniform within the PTV. [Methods] We modeled the linear energy transfer (LET) dependence of the linear-quadratic (LQ) coefficients specific to prostate cancer, which accounts for the majority of CIRT. This was achieved by irradiating prostate cancer cells (PC3) with X-rays from a 4 MV-Linac and carbon beams with different LETs of 11.1–214.3 keV/μm. By using the radiosensitivity of PC3 cells derived from cellular experiments, we reconstructed prostate-cancer-specific clinical dose distributions on patient computed tomography (CT). [Results] The LQ coefficient, α, of PC3 cells was larger than that of HSG cells at low (<50 keV/μm) LET and smaller at high (>50 keV/μm) LET, which was validated by cellular experiments performed on rectangular SOBPs. The reconstructed dose distribution on patient CT was sloped when 1 fraction incident from the one side of the patient was considered, but remained uniform from the sum of 12 fractions of the left–right opposing beams (as is used in clinical practice). [Conclusion] Our study reveals the inhomogeneity of clinical doses in single-field plans calculated using the PC3 radiosensitivity data. However, this inhomogeneity is compensated by using the combination of left–right opposing beams. [ABSTRACT FROM AUTHOR]

Prostate cancer is the major cause of cancer-related deaths worldwide in men. There are new treatment methods and drugs are being developed with promising results in two of the prostate cancer cell lines (PPC-1 and TSU-Pr1). These two cells were treated with 20 uM of axitinib combined with dasatinib for 6-72 hours. The cell viability assessed by the cytotoxicity assay. Various regulatory genes such as c-KIT, cell cycle and apoptosis and angiogenic factors were also studied. The enzyme activity of apoptosis effector caspase-3 was colorimetrically determined. Axitinib and dasatinib combination lowered the survival rate of PPC-1 cells but enhanced the survival rate of TSU-Pr1 cells. The protein expression levels in apoptosis and angiogenesis factors were also found to be in contrast between the two cell lines. PPC-1 and TSU-Pr1 cells displayed a different response to axitinib with dasatinib, which explains different expression levels of regulators of cell-cycle, apoptosis and angiogenesis.