Human Prostate Carcinoma Cell Line Research Articles

Flavonolignans and Biological Activity of Nannorrhops ritchiana Leaves

Objectives: This study aimed at isolating the polyphenolic compounds of 70% methanol extract ofNannorrhops ritchiana Griff. leaves and assaying the antioxidant and cytotoxic activities of the extract and main fractions. Methods: The methanol extract of the leaves of N. ritchiana was chromatographically fractionated using a bioactivity-guided approach. The isolated compounds were spectroscopically elucidated by UV, MS, 1H/13C NMR and 2D NMR spectroscopic techniques. The radical scavenging activity of the methanol extract and its fractions was evaluated using DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging assay and their cytotoxic activity was assayed using SRB (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide) test against human hepatocellular liver carcinoma (HepG2), human alveolar adenocarcinoma (A549) and human prostate carcinoma (PC3) cell lines. Results: Eight compounds were isolated and identified for the first time from the leaves of N. ritchiana, comprising five flavonolignans;Indocalatin A (4) which is a rare compound that has been reported only once in nature, 9″-O-glucopyranosyl Salcolin A (5), 9″-O-glucopyranosyl Salcolin B (6) together with their aglycones, Salcolin A (7) and Salcolin B (8) along with three flavone glycosides; Tricin-7-O-rutinoside (1), Orientin (2) and Isoorientin (3). The methanol extract of N. ritchiana showed antioxidant activity with SC50 39.4 ± 1.06 μg/ml, while fraction IIshowed significant effect with SC50 of 6.1 ± 0.24 μg/ml in comparison with ascorbic acid (SC50 1.8 ± 0.35 μg/ml). The methanol extract and the fraction III showed a promising cytotoxic activity against selected cell lines especially the A549 with IC50 9.5 ± 1.98 μg/ml and HepG2 with IC50 8.15 ± 1.3 μg/ml, respectively. Conclusion: N. ritchiana leaf methanol extract is a new source of biologically active compounds, including flavonolignans.

Insight on cytotoxic effects of silver nanoparticles: Alternative androgenic transactivation by adsorption with DHT

Silver nanoparticles (AgNPs) are accumulated in the male reproductive organs for a long time and cause several adverse effects in there. Up to now, there is little of information for the cytotoxic effects in male reproductive cells. In this study, the stable AgNPs with a minimal silver ion (Ag+) dissolution below concentration inducing cytotoxicity in the cell medium were exposed to the human prostate carcinoma cell line 22Rv1. Moreover particle uptake and androgen receptor (AR) transactivation were evaluated. In cell medium, AgNPs exhibited stability in an aqueous environment and minimal Ag+ release. Transmission electron microscopy (TEM) and energy dispersive spectrometer (EDS) analysis demonstrated uptake of AgNPs into cells via endocytosis, and a quantitative Ag assay showed that uptake of AgNPs was size-dependent with the majority of Ag retained in the particle form. To evaluate if the presence of AgNPs can change androgenic potentials of dihydrotestosterone (DHT, strong human androgen), we conducted an AR transactivation assay using the transgenic prostate cell line 22Rv1-MMTV-Hyg and found that AgNPs lowered androgenic transactivation of DHT, which is due to decreased bioavailability of DHT.

Effect of Levisticum officinale Hydroalcoholic Extract on DU-145 and PC-3 Prostate Cancer Cell Lines

: Levisticum officinale contains a variety of components used for its medicinal properties in traditional medicine. The previous studies showed that it had an anti-cancer effect on cell lines. The current study aims to evaluate the cytotoxic potential of Levisticum officinale hydroalcoholic extract (LOHE) on DU-145 and PC-3 human advanced prostate cancer cell lines. The anti-proliferative activity of LOHE was evaluated using the MTT assay. The results of MTT showed that the IC50 of DU-145 and PC-3 were 500 µg/mL and 400 µg/mL of LOHE, respectively, following 24 hours treatment. This study found that the hydroalcoholic extract of Levisticum officinale had beneficial cell death inducing effects on both the PC3 and DU145 human prostate carcinoma cell lines in time- and concentration-dependent fashion. Hence, LOHE may have remarkable potential for uses as new natural anticancer agent.

The 22Rv1 prostate cancer cell line carries mixed genetic ancestry: Implications for prostate cancer health disparities research using pre-clinical models.

Understanding how biological factors contribute to prostate cancer (PCa) health disparities requires mechanistic functional analysis of specific genes or pathways in pre-clinical cellular and animal models of this malignancy. The 22Rv1 human prostatic carcinoma cell line was originally derived from the parental CWR22R cell line. Although 22Rv1 has been well characterized and used in numerous mechanistic studies, no racial identifier has ever been disclosed for this cell line. In accordance with the need for racial diversity in cancer biospecimens and recent guidelines by the NIH on authentication of key biological resources, we sought to determine the ancestry of 22RV1 and authenticate previously reported racial identifications for four other PCa cell lines. We used 29 established Ancestry Informative Marker (AIM) single nucleotide polymorphisms (SNPs) to conduct DNA ancestry analysis and assign ancestral proportions to a panel of five PCa cell lines that included 22Rv1, PC3, DU145, MDA-PCa-2b, and RC-77T/E. We found that 22Rv1 carries mixed genetic ancestry. The main ancestry proportions for this cell line were 0.41 West African (AFR) and 0.42 European (EUR). In addition, we verified the previously reported racial identifications for PC3 (0.73 EUR), DU145 (0.63 EUR), MDA-PCa-2b (0.73 AFR), and RC-77T/E (0.74 AFR) cell lines. Considering the mortality disparities associated with PCa, which disproportionately affect African American men, there remains a burden on the scientific community to diversify the availability of biospecimens, including cell lines, for mechanistic studies on potential biological mediators of these disparities. This study is beneficial by identifying another PCa cell line that carries substantial AFR ancestry. This finding may also open the door to new perspectives on previously published studies using this cell line.

Co-assembled hybrids of proteins and carbon dots for intracellular protein delivery

Silver nanoparticles (AgNPs) are accumulated in the male reproductive organs for a long time and cause several adverse effects in there. Up to now, there is little of information for the cytotoxic effects in male reproductive cells. In this study, the stable AgNPs with a minimal silver ion (Ag+) dissolution below concentration inducing cytotoxicity in the cell medium were exposed to the human prostate carcinoma cell line 22Rv1. Moreover particle uptake and androgen receptor (AR) transactivation were evaluated. In cell medium, AgNPs exhibited stability in an aqueous environment and minimal Ag+ release. Transmission electron microscopy (TEM) and energy dispersive spectrometer (EDS) analysis demonstrated uptake of AgNPs into cells via endocytosis, and a quantitative Ag assay showed that uptake of AgNPs was size-dependent with the majority of Ag retained in the particle form. To evaluate if the presence of AgNPs can change androgenic potentials of dihydrotestosterone (DHT, strong human androgen), we conducted an AR transactivation assay using the transgenic prostate cell line 22Rv1-MMTV-Hyg and found that AgNPs lowered androgenic transactivation of DHT, which is due to decreased bioavailability of DHT.

Zinc distribution in human prostate carcinoma cell line using synchrotron X‐ray microfluorescence

Cancer is a worldwide public health problem, and its incidence in the world grew by 20% in the last decade. Zinc, an essential trace element, is involved in many cellular processes. Concerning prostate cancer, Zn could inhibit the growth of tumor cells, by inducing cell cycle arrest or apoptosis. X‐ray microfluorescence (μXRF) is an elemental analysis technique that allows mapping biologically important elements at a submillimeter scale, with high sensitivity and negligible damage to the sample. In this study, we investigated cell viability through colorimetric cytotoxicity assay (MTT) and the behavior of human prostate cell lines obtained from normal (RWPE‐1) and tumorigenic (DU145) epithelium, in three‐dimensional spheroid cultures after supplementation with ZnCl2 for 24 and 48 hr using synchrotron μXRF. The measurements were performed at the Synchrotron Light National Laboratory (Campinas, Brazil). The results of μXRF showed that Zn intensity decreased in the DU145 tumor cells independent of supplementation or treatment time, and in normal cells, the intensity increased with supplementation and treatment time. The MTT assay results showed no significant differences, which indicates that the cell viability did not change. Our results indicate that μXRF can be used as an important tool to understand the mechanism of the loss of ability to capture zinc by prostate cancer cells. Copyright © 2017 John Wiley & Sons, Ltd.

Procyanidins from Vitis vinifera seeds induce apoptotic and autophagic cell death via generation of reactive oxygen species in squamous cell carcinoma cells.

Procyanidins can inhibit cell proliferation and tumorigenesis and induce apoptosis in human skin, breast and prostate carcinoma cell lines. Squamous cell carcinoma (SCC) of the skin is a common form of keratinocytic or non-melanoma skin cancer and is a deadly disease with a poor prognosis due to the ineffectiveness of therapy. The present study aimed to determine whether grape seed proanthocyanidin (GSP) may regulate different modes of cell death in the human SCC12 cell line. The present study found that the treatment of SCC12 cells with GSP inhibited proliferation in a dose-dependent manner and reduced the motility and invasiveness of SCC12 cells through suppression of matrix metalloproteinase-2/9 expression. GSP treatment also resulted in induction of apoptosis and autophagy via generation of reactive oxygen species. The inhibition of autophagy by 3-methyladenine decreased GSP-induced cell death, which suggested that GSP-induced autophagy can promote cell death. The results of the present study suggested that autophagy functions as a death mechanism in SCC and provided a rationale for the use of GSP in combination with autophagy activators for treating cancers such as SCC.

Involvement of apoptotic pathways in docosahexaenoic acid-induced benefit in prostate cancer: Pathway-focused gene expression analysis using RT2 Profile PCR Array System

BackgroundPresent study aimed to better understand the potential apoptotic pathways that involved in docosahexaenoic acid (DHA)-induced apoptosis of prostate cancer cells.MethodsHuman prostate cancer DU145 cells were treated with different concentrations of fish oil, omega-3 PUFA (DHA, and Eicosapentaenoic acid, EPA), or omega-6 PUFA (Arachidonic acid, AA). Cell viability and apoptosis were evaluated by MTT assay and Hoechst staining. Pathway-focused gene expression profiling of DU145 cells was analyzed with the RT2 Profile PCR Array System. The results were verified by real time quantitative polymerase chain reaction (RT-qPCR).ResultsAA exposure showed no obvious effect on viability of DU145 cells. However, exposure with fish oil, EPA, or DHA for 24 h significantly affected cell viability. The growth inhibition of DHA was more pronounced than that of EPA and showed a time-dependent increase. DHA exposure caused typical apoptotic characteristics. Ten genes were more expressed, while 5 genes were less expressed following DHA exposure. RT-qPCR confirmed the time dependent effect of DHA on the expression of these differentially expressed genes. KEGG pathway analysis showed that DHA may induce the apoptosis of cancer cells preferentially through mediating P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways.ConclusionOur study demonstrated the beneficial action of DHA on human prostate carcinoma cell line DU145. The pro-apoptotic effect of DHA on DU145 cells may involve mediation various pathways, especially P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways. Molecular mechanisms of DHA on apoptosis of cancer cells still need to be further clarified.

Serotonin receptor 4 (5-hydroxytryptamine receptor Type 4) regulates expression of estrogen receptor beta and cell migration in hormone-naive prostate cancer.

Estrogens are considered to potentially play some roles in the development and progression of prostate cancer through estrogen receptor beta (ERβ). However, additional factors which could influence the clinical outcome of the patients through modulating these steroid signalings have also been proposed. Among these, increased expression of serotonin receptor especially that of 5-hydroxytryptamine receptor Type 4 (5-HTR4) has been recently proposed to be involved in autocrine/paracrine mechanisms of castration-resistant prostate cancer, but the presence and clinical significance of 5-HTR4 in hormone-naive prostate cancer (HNPC) and its interaction with hormonal signaling pathways have remained virtually unknown. We evaluated the status of 5-HTR4 in 112 human HNPC cases (acinar adenocarcinoma) using immunohistochemistry and correlated the findings with clinicopathological features of individual patients and the status of androgen receptor (AR) and ERβ. To further elucidate its underlying mechanisms, androgen-dependent human prostate carcinoma cell line, LNCaP, expressing 5-HTR4, was treated by 5-HTR4 agonist. 5-HTR4 immunoreactivity was detected in 34% of prostate cancer cases examined (38/112) and was significantly correlated with the status of ERβ but not with that of AR and other clinicopathological factors of the patients. Results of in vitro studies demonstrated that 24 h incubation with 5-HTR4 agonist (10 nM) increased the expression level of ERβ messenger RNA compared to controls. 5-HTR4 agonist (100 nM) significantly inhibited LNCaP carcinoma cell migration (P < 0.05). Results of our present study indicated that 5-HTR4 signaling upregulated ERβ expression in HNPCs and could impact on biological processes in HNPC.

Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.

Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines. The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP.

Evaluation of anticancer activity of Cordia dichotoma leaves against a human prostate carcinoma cell line, PC3

Mechanisms of antioxidant and apoptosis induction may be involved in the management of cancer by medicinal plants. Aim of the study was designed to evaluate anticancer activity of the methanolic extract of Cordia dichotoma leaves (MECD) against a human prostate carcinoma cell line, PC3. Flavonoid content was determined by colorimetric principle and antioxidant activity by various in vitro assays. MTT, DCFH-DA and DAPI staining assays were performed for the evaluation of cytotoxicity, analysis of induction of apoptosis and intracellular reactive oxygen species (ROS) activity level by MECD against human prostate carcinoma cell line, PC3. Flavonoid content was found to be 160 mg QE/g extract. IC50 values for MECD treatment in various assays based on scavenging of 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid), nitric oxide, peroxy radical, superoxide anion, hydroxy radical were found to be 315.5, 38, 476, 523, 197, 82 μg/ml respectively. MECD exposure to PC3 cells significantly increased the cell death (p < 0.001, IC50 = 74.5 μg/ml), nuclear condensation, apoptosis (p < 0.001) and induced production of ROS (p < 0.001) initiating apoptotic cascade in a dose dependent manner. This study confirms that MECD possesses antioxidant property and can prevent carcinogenesis by reducing oxidative stress. MECD possesses anticancer activity and lead to PC3 cell death via induction of apoptosis mediated through excessive ROS generation. Flavonoids in MECD may be responsible for these activities due to dual antioxidant and pro-oxidant properties.

Apium graveolens Extract Inhibits Cell Proliferation and Expression of Vascular Endothelial Growth Factor and Induces Apoptosis in the Human Prostatic Carcinoma Cell Line LNCaP.

Apium graveolens has been shown to inhibit the growth of a variety of cancer tissues. In this study, we investigated the anticancer effect of A. graveolens on the human prostatic carcinoma cell line LNCaP. LNCaP cells were treated with increasing concentrations of an ethanolic extract of A. graveolens ranging from 1000 to 3000 μg/mL, and viability was determined after 24 and 48 h using the XTT cell proliferation assay. The levels of cleaved poly (ADP-ribose) polymerase (PARP), one of the best biomarkers of apoptosis, were analyzed. Finally, quantitative gene expression analysis of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis, was performed using real-time reverse transcription-polymerase chain reaction. A. graveolens extract inhibited cell viability in both a time- and dose-dependent manner. Data from cleaved PARP assays suggested that A. graveolens caused induction of apoptosis in these cells. Treatment of cells with A. graveolens also resulted in downregulation of VEGF expression. This study showed that the antiproliferative effect exerted by an ethanolic extract of A. graveolens is triggered by induction of apoptosis. We also demonstrated that VEGF expression was downregulated by treatment with A. graveolens extract.

High-Content Screening Identifies Src Family Kinases as Potential Regulators of AR-V7 Expression and Androgen-Independent Cell Growth.

AR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood. Therefore, we aimed to explore existing classes of small molecules that may regulate AR-V7 expression and intracellular localization and their potential therapeutic role in CRPC. We used AR high-content analysis (AR-HCA) to characterize the effects of a focused library of well-characterized clinical compounds on AR-V7 expression at the single-cell level in PC3 prostate cancer cells stably expressing green fluorescent protein (GFP)-AR-V7 (GFP-AR-V7:PC3). In parallel, an orthogonal AR-HCA screen of a small interfering (si)RNA library targeting 635 protein kinases was performed in GFP-AR-V7:PC3. The effect of the Src-Abl inhibitor PD 180970 was further characterized using cell-proliferation assays, quantitative PCR, and western blot analysis in multiple hormone-sensitive and CRPC cell lines. Compounds that tended to target Akt, Abl, and Src family kinases (SFKs) decreased overall AR-V7 expression, nuclear translocation, absolute nuclear level, and/or altered nuclear distribution. We identified 20 protein kinases that, when knocked down, either decreased nuclear GFP-AR-V7 levels or altered AR-V7 nuclear distribution, a set that included the SFKs Src and Fyn. The Src-Abl dual kinase inhibitor PD180970 decreased expression of AR-V7 by greater than 46% and decreased ligand-independent transcription of AR target genes in the 22RV1 human prostate carcinoma cell line. Further, PD180970 inhibited androgen-independent cell proliferation in endogenous-AR-V7-expressing prostate cancer cell lines and also overcame bicalutamide resistance observed in the 22RV1 cell line. SFKs, especially Src and Fyn, may be important upstream regulators of AR-V7 expression and represent promising targets in a subset of CRPCs expressing high levels of AR-V7. Prostate 77:82-93, 2017. © 2016 Wiley Periodicals, Inc.

Autoregulated expression of p53 from an adenoviral vector confers superior tumor inhibition in a model of prostate carcinoma gene therapy

ABSTRACTAlternative treatments for cancer using gene therapy approaches have shown promising results and some have even reached the marketplace. Even so, additional improvements are needed, such as employing a strategically chosen promoter to drive expression of the transgene in the target cell. Previously, we described viral vectors where high-level transgene expression was achieved using a p53-responsive promoter. Here we present an adenoviral vector (AdPGp53) where p53 is employed to regulate its own expression and which outperforms a traditional vector when tested in a model of gene therapy for prostate cancer. The functionality of AdPGp53 and AdCMVp53 were compared in human prostate carcinoma cell lines. AdPGp53 conferred greatly enhanced levels of p53 protein and induction of the p53 target gene, p21, as well as superior cell killing by a mechanism consistent with apoptosis. DU145 cells were susceptible to induction of death with AdPGp53, yet PC3 cells were quite resistant. Though AdCMVp53 was shown to be reliable, extremely high-level expression of p53 offered by AdPGp53 was necessary for tumor suppressor activity in PC3 and DU145. In situ gene therapy experiments revealed tumor inhibition and increased overall survival in response to AdPGp53, but not AdCMVp53. Upon histologic examination, only AdPGp53 treatment was correlated with the detection of both p53 and TUNEL-positive cells. This study points to the importance of improved vector performance for gene therapy of prostate cancer.

PHYTOCHEMICAL AND BIOLOGICAL STUDIES ON PERSICARIA SALICIFOLIA BROUSS. EX WILLD GROWING IN EGYPT

The phytochemical investigation of Persicaria salicifolia Brouss. ex Willd herb resulted in isolation of trans phytol, β-sitosterol, β-sitosterol-3-OD-glucoside, luteolin, quercetin, quercitrin, hyperoside and rutin. The compounds were isolated using different chromatographic techniques. The isolated compounds were identified using different spectroscopic techniques including UV, IR, MS, HNMR and CNMR.The antitumor effect of total ethanolic extract of Persicaria salicifolia herb against solid Ehrlich carcinoma (SEC) was examined and the results revealed that the extract has strong antitumor activity. In vitro cytotoxic assay against human breast carcinoma (MCF-7) and prostate carcinoma (PC3) cell lines was carried out using different fractions of alcoholic extract. Methylene chloride and ethyl acetate fractions exhibited the highest activity against breast carcinoma, while petroleum ether extract exhibited the highest activity against prostate carcinoma cell line. Phytol, luteolin and quercitrin were isolated for the first time from Persicaria salicifolia Brouss. ex Willd.

Peptide-conjugated nanoparticles for targeted imaging and therapy of prostate cancer

While there has been extensive development of anti-cancer drugs for treatment of prostate cancer, the therapeutic efficacy of such drugs remains inadequate in many cases. Here, we performed in vitro biopanning of the PC3 human prostate carcinoma cell line to select prostate cancer-specific peptides by phage display. We successfully identified specific peptides targeting prostate cancer cells, and their specificity was confirmed by cellular ELISA and flow cytometry. Moreover, we found that the phage clones also recognize other prostate cancer cell lines and surgical specimens from prostate cancer patients. The tumor targeting ability of these phages was validated in a xenograft model, in which high accumulation of targeting phage was observed. To investigate whether selected peptides are able to target tumors and enhance drug delivery into cancer cells, we synthesized peptide-PEGylated lipids and post-inserted them into preformed liposomal doxorubicin and vinorelbine. The results of our cellular uptake and MTT assays indicate that peptide-conjugated liposomes exhibit enhanced drug intracellular delivery and cytotoxicity. The conjugation of targeting peptide to imaging agents, such as quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs), results in more precise delivery of these agents to tumor sites. Furthermore, administration of liposomal doxorubicin and vinorelbine conjugated with targeting peptides was found to markedly increase the inhibition of human prostate tumor growth in mouse xenograft and orthotopic models. These results indicate that targeting peptide, SP204, has significant potential for targeted therapy and molecular imaging in prostate cancer.

Biosynthesis of gold decorated reduced graphene oxide and its biological activities

An eco-friendly, very simple method for synthesis of gold-reduced graphene oxide (Au-rGO) nanocomposite was developed using fruit of Piper pedicellatum C.DC. Its characterization was done by UV–visible, FT-IR, XRD, XPS, Raman, SEM-EDX, TEM analysis. The antibacterial activity of Au-rGO nanoparticles was investigated against the Gram negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Gram positive bacteria Staphylococcus aureus and Bacillus cereus. In addition, in-vitro cell based cytotoxicity study was performed for Au-rGO and GO against PC3 (aggressive human prostate carcinoma cell line) and RWPE-1(non-malignant human prostate epithelial cells). Cytotoxicity assay revealed that Au-rGO is more toxic than GO nanoparticles against PC3 cancer cells compared to RWPE-1

Formation of intracellular lumina in human prostate carcinoma (DU145) cells, maturation into signet cells, and the cribriform morphology of tumors

ABSTRACTThe intracellular or intracytoplasmic lumen (IL) is an enigmatic histological structure that occurs in various tumor cells. A reassessment of diverse ILs fine-structure micrographs obtained out of previous studies encompassing the human prostate carcinoma (DU145) cell line and xenotransplanted carcinomas enabled us to propose aspects of ILs development in cancer cells: a combination of altered expressions in intercellular contacts and their cytoskeletal components would favor a disarray of self-apical polarity orientation; those defects, associated with a local, entwined enriched membranous structures growing as microvilli-like formations out of a disrupted endoplasm and trans-Golgi sorting, create ILs in cells’ perikarya. These misplaced intracytoplasmic domains can become enlarged through spaces made between the finger-like structures by accruing membranes of coalescent intracytoplasmic vesicles then adding microvilli and glycocalyx to constitute ILs. Cationic mucins added with or without a progressive or total loss of microvilli and content generate signet or ring cell, while ILs enlarge. Variable build-ups of these cells’ populations in carcinomas result in architectural mix-up of adjacent cells around these voids, misconstrued as new lumen, and establish a “cribriform” tumor pattern that often implies a poor cancer prognosis. Alternatively, cytotoxic changes caused by anticancer pro-oxidant treatment favor membrane alterations and exaggerate the ILs in xenotransplants into intracellular crypts that accompany other tumor degenerative changes.

Talarolutins A–D: Meroterpenoids from an endophytic fungal isolate of Talaromyces minioluteus

Four meroterpenoids [talarolutins A–D] and one known compound [purpurquinone A] were characterized from an endophytic fungal isolate of Talaromyces minioluteus (G413), which was obtained from the leaves of the medicinal plant milk thistle [Silybum marianum (L.) Gaertn. (Asteraceae)]. The structures of talarolutins A–D were determined by the analysis of various NMR and MS techniques. The relative and absolute configuration of talarolutin A was determined by X-ray diffraction analysis. A combination of NOESY data and comparisons of ECD spectra were employed to assign the relative and absolute configuration of the other analogs. Talarolutins B–D were tested for cytotoxicity against human prostate carcinoma (PC-3) cell line, antimicrobial activity, and induction of quinone reductase; no notable bioactivity was observed in any assay.

5-Bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one targets prostate cancer cells by down-regulating inflammation-related genes

&lt;p class="Abstract"&gt;The present study was performed to examine the effect of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on the rate of cell proliferation and apoptosis induction in the PC3, human prostate carcinoma cell line. The cell viability was assayed by using sulphorhodamine B staining and apoptosis by annexin V and flow cytometry analyses. The results revealed that BHP treatment in PC3 cells caused a significant reduction in the rate of cell proliferation in dose- and time-dependent manner. Compared to the un-treated cells, the formation of HUVEC tubes was markedly inhibited on treatment with BHP at a concentration of 30 µM. Further investigation revealed the expression of HMGB1, IL-6 and IL-8, pro-inflammatory cytokines was also inhibited on treatment with BHP. Therefore, BHP treatment plays an important role in inducing apoptosis in the prostrate cells and can be of therapeutic value for the prostate cancer treatment.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;