Rat Prostate Cancer Research Articles

CRISPR-Cas9 genome and long non-coding RNAs as a novel diagnostic index for prostate cancer therapy via liposomal-coated compounds.

CRISPR/Cas9 is a recently discovered genomic editing technique that altered scientist's sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2'- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2'- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including MALAT1. On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR/Cas9 gene editing and long non coding gene MALAT1.

Lidocaine Inhibits Rat Prostate Cancer Cell Invasiveness and Voltage-Gated Sodium Channel Expression in Plasma Membrane.

There is increasing evidence, mostly from breast cancer, that use of local anaesthetics during surgery can inhibit disease recurrence by suppressing the motility of the cancer cells dependent on inherent voltage-gated sodium channels (VGSCs). Here, the possibility that lidocaine could affect cellular behaviours associated with metastasis was tested using the Dunning cell model of rat prostate cancer. Mostly, the strongly metastatic (VGSC-expressing) Mat-LyLu cells were used under both normoxic and hypoxic conditions. The weakly metastatic AT-2 cells served for comparison in some experiments. Lidocaine (1-500μM) had no effect on cell viability or growth but suppressed Matrigel invasion dose dependently in both normoxia and hypoxia. Used as a control, tetrodotoxin produced similar effects. Exposure to hypoxia increased Nav1.7 mRNA expression but VGSCα protein level in plasma membrane was reduced. Lidocaine under both normoxia and hypoxia had no effect on Nav1.7 mRNA expression. VGSCα protein expression was suppressed by lidocaine under normoxia but no effect was seen in hypoxia. It is concluded that lidocaine can suppress prostate cancer invasiveness without effecting cellular growth or viability. Extended to the clinic, the results would suggest that use of lidocaine, and possibly other local anaesthetics, during surgery can suppress any tendency for post-operative progression of prostate cancer.

Assessment of the in-vitro toxicity and in-vivo therapeutic capabilities of Juglans regia on human prostate cancer and prostatic hyperplasia in rats

Benign prostatic hyperplasia (BPH) and prostatic cancer are aging-associated urological conditions in men. While significant advances have been made in relation to treatment, poor response, treatment resistance and adverse side-effects limit currently available therapies. The possible antiproliferative and/or ameliorative potentials of Juglans regia have been reported, however, there is a dearth of scientific information on its effect on BPH or prostatic cancer. In this study, in-vivo and in-vitro studies were used to assess the possible benefits of fresh walnut fruits extract in BPH or prostate cancer. High-performance liquid chromatography coupled with electro spray ionization and quadrupole-time-of-flight mass spectrometry (HPLC-ESI-Q-TOF) was used to assess the chemical profile of the plant extract. The anti-proliferative activity of Juglans regia extract was tested against normal and cancerous human prostate cell lines by using the iCELLigence real-time and label-free cell analysis system. The ameliorative potential of fresh fruits Juglans regia extract was assessed by administering the extract at 50 and 100 mg/kg body weight to rats with testosterone induced BPH. Analysis of phytochemicals in Juglans regia revealed a high concentration of phenolic acids and flavonoids, Juglans regia also showing time- and dose-dependent anti-proliferative activity against prostate cancer cells, and reversed biochemical and histomorphological changes induced by testosterone-induced BPH.

Paclitaxel nanocrystals carrying miR-200c inhibit prostate cancer in rats by regulating forkhead box protein O (FOXO) activity

Prostate cancer is a malignant tumor in the male reproductive organs. Its incidence is increasing year by year, and therefore, this study investigated regulatory effect of paclitaxel nanocrystals on forkhead box protein O (FOXO) activity in rats with prostate cancer. Firstly, paclitaxel nanocrystals carrying miRNA-200c were synthesized. Nine rats in the model control group were used to establish a tumor-bearing model. The rats were intervened with miRNA-200c in the miRNA-200c group on the basis of model group, and treated with paclitaxel nanosuspension in the paclitaxel nano group. The rats were intervened with paclitaxel nano and miRNA-200c in the paclitaxel nano+miRNA-200c group. Tumor inhibition rates were measured, and tumor cell morphology was assessed by hematoxylin-eosin (HE) staining, while cell behaviors were detected by CCK-8, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), AnnexinV-Fluorescein isothiocyanate (FITC), and Transwell methods, which were used to analyze miRNA-200c and FOXO levels. Paclitaxel nanocrystals carrying miR-200c (PN-miR-200c) significantly slowed down the growth rate of prostate cancer. In addition, it also reduced the viability, proliferation and invasion of rat PC3 cells, and increased cell apoptosis. On the other hand, PN-miR-200c further increased FoxO mRNA expression by activating FoxO pathway. The bioinformatics software RegRNA 2.0 predicted that, the specific target gene that may be regulated by miR-200c is FoxO, which confirmed that, the miR-200c has a targeting relationship with FoxO. PN-miR-200c can activate FOXO pathway, up-regulate FoxO, reduce the biological behaviors of rat PC3 cells, increase apoptosis, and ameliorate histopathological damage, providing new ideas for clinical treatment of prostate cancer.

Cucumis sativus (Cucurbitaceae) seed oil prevents benzo(a)pyrene-induced prostate cancer in vitro and in vivo.

Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C. sativus (CS) seed oil and its possible chemopreventive potential on benzo(a)pyrene (BaP)-induced PCa in Wistar rat. In vitro cell growth, clone formation, cell death mechanism, cell adhesion and migration as well as expression of integrins β-1 and β-4 were assessed. In vivo PCa was induced in 56 male rats versus 8 normal control rats, randomized in normal (NOR) and negative (BaP) control groups which, received distilled water; the positive control group (Caso) was treated with casodex (13.5 mg/kg BW). One group received the total seed extract at the dose of 500 mg/kg BW; while the remaining three groups were treated with CS seed oil at 42.5, 85, and 170 mg/kg BW. The endpoints were: morphologically (prostate tumor weight and volume), biochemically (total protein, prostate specific antigen (PSA), oxidative stress markers such as MDA, GSH, catalase, and SOD) and histologically. As results, CS seed oil significantly and concentration-dependently reduced the DU145 prostate cancer cell growth and clone formation (optimum = 100 μg/mL). It slightly increased the number of apoptotic cells and inhibited the migration and invasion of DU145 cells, while it decreased their adhesion to immobilized collagen and fibrinogen. The expression of integrin β-1 and β-4 was increased in presence of 100 μg/mL CS oil. In vivo, the BaP significantly elevated the incidence of PC tumors (75%), the total protein and PSA levels, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and MDA levels compared to NOR. CS seeds oil significantly counteracted the effect of BaP by decreasing significantly the PC incidence (12.5%), and increasing the level of antioxidant (SOD, GSH, and catalase) and anti-inflammatory cytokine IL-10 in serum. While in BaP group PCa adenocarninoma was the most representative neoplasm, rats treated with 85 and 170 mg/kg prevented it in the light of the casodex. It is conclude that CS may provide tumor suppressive effects in vitro and in vivo which makes it an interesting candidate to support the current treatment protocol.

Inhibition Effect of Cell-Free Supernatants of Environmental Acanthamoeba Strains on the Viability of Metastatic Cell-Lines

It is known that some of the therapeutic agents against cancer cells are isolated from natural sources such as plants and animals. However, due to increasing drug resistance, studies on the discovery of new sources are needed. In this study, it was aimed to investigate the inhibition effects of four native Acanthamoeba strains on different cancer cell lines (MDA-MB-231, PC3, MAT-LyLu). 3T3 cells were used as normal cell line. All strains were recultured by using non-nutrient agar spread by heat-inactivated Escherichia coli ATCC 25922. A.castellanii ATCC 50373 was used as the standard strain. Molecular identification of the native Acanthamoeba isolates was done by polymerase chain reaction (PCR) and DNA sequence analysis using specific primer pairs (P-FLA-F, P-FLA-R, JDP-F, JDP-R). Axenic cultures of all strains were obtained in 25 cm2 tissue culture flasks and in peptone yeast extract glucose (PYG) medium. In order to investigate the effect of cell-free supernatants obtained from axenic cultures on cancer cell lines and 3T3 cell viability, MTT method was applied using different concentrations of cell-free supernatants (1%, 2%, 5%, 10%, 15%). It was determined that the viability of 3T3 cells was not affected by any Acanthamoeba cell-free supernatants (p≤ 0.05). All of the samples tested were found to have a significant inhibitory effect (p<0.05) on the viability of PC3 and MAT-LyLu cells (human and rat prostate cancer cell line). However, none of the samples had an inhibitory effect on the viability of MDA-MB-231 (breast cancer cell-line). Two native Acanthamoeba cell-free supernatants showed higher inhibitory potency (28% and 21.9%) at 2% concentration against PC3 cells compared to the reference strain (16%). Similarly, the same Acanthamoeba samples were also shown to have a better inhibition potential on the viability of MAT-LyLu cells than the reference strain. It was found that the inhibitory potential of Acanthamoeba cell-free supernatants may not be related to proteins and proteases. The results obtained from this study showed that Acanthamoeba species living in the aquatic environment isolated from our country have a potential inhibitory effect against the tested cancer cell lines. In addition to plants and animals, Acanthamoeba cell-free supernatants can also be a source for natural therapeutic substances that act against cancer cells. However, it is necessary to carry out new studies using more strains in order to detect strains with higher inhibitory effects.

Hormonal and genotoxic estrogen-androgen carcinogenesis in the NBL rat prostate: A role for aromatase.

Androgens are generally thought to cause prostate cancer, but the data from animal studies suggest that they must be aromatized to estrogen and act in concert with genotoxic estrogen metabolites. The objective of this study was to determine whether treatment with testosterone (T) combined with a nonestrogenic estrogen metabolite and a nongenotoxic estrogenic compound would all be necessary and sufficient for the induction of a high incidence of prostate cancer in the susceptible NBL rat strain. NBL rats were treated with low-dose testosterone via slow-release Silastic implants and with the marginally estrogenic genotoxic catechol estrogen 4-hydroxyestradiol (4OH-E2) and the nongenotoxic estrogen 2-fluoroestradiol (2F-E2) and in one experiment the aromatase inhibitor letrozole via custom-made slow-release pellets. Animals were euthanized 52 weeks after implantation and their pituitaries and prostate complexes weighed and fixed in formalin. Hematoxylin and eosin (H&E)-stained step sections were prepared and examined microscopically for proliferative lesions. Animals treated with 2F-E2, with or without the other compounds, had enlarged pituitaries demonstrating its estrogenicity. Animals treated with T, with or without the other compounds, had enlarged prostates consistent with its androgenicity. Rats treated with T plus 2F-E2 and 4OH-E2 developed a high incidence of prostatic cancer (89%), while, surprisingly, rats treated with T plus only 2F-E2 also had a high incidence of prostate cancer (95%) contradicting our initial hypothesis. To test whether the formation of E2 from T by aromatase could lead to estrogen genotoxicity and prostate carcinogenesis we then rats treated with T and 2F-E2 also with letrozole and found that it reduced prostate cancer incidence by about 50%. These findings indicate that long-term treatment with a nongenotoxic estrogen (2F-E2) and T as well as uninhibited prostatic aromatase activity generating genotoxic E2 are all required for induction of a high incidence of prostatic adenocarcinomas in NBL rats. These and previous data indicate that androgen receptor-mediated action, estrogen receptor mediation, and estrogen genotoxicity are all required and sufficient for hormonal carcinogenesis in the NBL rat prostate. Interference with the estrogen genotoxicity is a potential approach to prostate cancer chemoprevention.

Toward tryptathionine-stapled one-bead-one-compound (OBOC) libraries: solid phase synthesis of a bioactive octretoate analog.

New somatostatin analogs are highly desirable for diagnosing and treating neuroendocrine tumors (NETs). Here we describe the solid-phase synthesis of a new octreotate (TATE) analog where the disulfide bond is replaced with a tryptathionine (Ttn) staple as part of an effort to prototyping a one-bead-one-compound (OBOC) library of Ttn-stapled peptides. Library design provides the potential for on- and off-bead screening. To validate our method, we labelled Ttn-TATE with a fluorescent dye to demonstrate binding to soluble somatostatin receptor subtype-2 and staining of Ar42J rat prostate cancer cells. By exploring this staple in the context of a ligand of known affinity, this method paves the way for an OBOC library construction of bioactive octreotate analogs and, more broadly speaking, tryptathionine-staped peptide macrocycles.

Appraising Animal Models of Prostate Cancer for Translational Research: Future Directions.

The growing incidence of prostate cancer has prompted a great investment in basic biology and translational studies to develop new therapies. Multiple animal models have been established to study etiological factors, cancer-preventive strategies and the molecular determinants of aggressiveness and metastases. The rat model of prostate cancer induced by chemical carcinogen N-methyl-N-nitrosourea (MNU) and testosterone exposure has become an important tool to study prostatic carcinogenesis and chemopreventive approaches. Over prolonged treatment, this model develops prostatic lesions that closely mimic those observed in human patients. By modifying the experimental conditions, different research groups have been able to induce a vast spectrum of lesions, ranging from early prostatic intraepithelial neoplasia to metastatic cancer. These carefully tuned experimental settings allowed researchers to test lifestyle interventions, and different pharmacological and chemopreventive strategies. However, this model's great flexibility requires careful planning to ensure that the experimental conditions are adequate to obtain the spectrum of lesions intended. The present review addresses such issues, highlighting the value of the rat prostate cancer model and the multiple challenges and opportunities it offers to researchers worldwide.

Effects of perinatal exposure to bisphenol A on induction of prostate cancer in Sprague Dawley rats by MNU and testosterone

Perinatal and neonatal exposure to bisphenol A (BPA) has been linked to enhancement of prostate carcinogenesis in rats induced by combined treatment with estradiol and testosterone, but human data are lacking. This study aimed to determine the effects of perinatal BPA exposure on induction of prostate cancer in rats by sequential treatment with N-methyl-N-nitrosamine (MNU) and continuous low dose administration of testosterone. Pregnant Sprague Dawley rats were exposed to BPA administered by subcutaneous Alzet minipumps at doses of 2.5 or 25 µg/kg body weight/day from gestational day 9 until postnatal day 28 when pups were weaned providing exposure of offspring in utero and via the mother’s milk. At 10–12 weeks of age, one male offspring per litter was treated with an intraperitoneal injection of MNU after hormonal stimulation of prostatic cell proliferation followed two weeks later by subcutaneous insertion of Silastic implants containing testosterone until the termination of the study 57–58 weeks after MNU injection. The perinatal BPA exposure did not significantly affect the incidence of prostate carcinomas which was slightly lower in exposed rats (33–23 %) than in control animals (40 %). Carcinomas in all accessory sex glands combined were also insignificantly less frequent in exposed (46–48 %) than in control rats (60 %). The incidence of malignant tumors at any site in the body was significantly lower in exposed rats (81–65 %) than in controls (93 %). In conclusion, perinatal BPA exposure did not significantly modify prostate cancer induction by MNU plus testosterone in rats, unlike the enhancement of prostate carcinogenesis induced by treatments involving estradiol administration. Which of the two models of prostate carcinogenesis is more relevant for the human situation is unclear at present.

Acidic Exo-Polysaccharide Obtained from Bacillus sp. NRC5 Attenuates Testosterone-DMBA-Induced Prostate Cancer in Rats via Inhibition of 5 α-Reductase and Na+/K+ ATPase Activity Mechanisms

Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product feasible for prostate cancer therapies. The anti-prostate cancer of acidic exo-polysaccharide produced from marine Bacillus sp. NRC5 (EBPS) was determined using 7,12-dimethylbenz-(a)-anthracene; DMBA-induced prostate cancer in male Sprague Dawley rats. Rats were subcutaneously injected with testosterone (3 mg/kg/day for 3 months) and a single dose of DMBA (65 mg/kg) for induction of prostate cancer. EBPS was administrated orally at dose 200 mg/kg/day for 3 months. To study protective effect of EBPS, animals received EBPS before cancer induction, meanwhile in therapeutic effect animals received EBPS after cancer induction. EBPS debug oxidative stress and inflammatory conditions associated with prostate cancer. EBPS either protective or therapeutic material considerably reduced cancer growth rate-limiting enzyme—i.e., 5-α-reductase (46.89 ± 1.72 and 44.86 ± 2.56 µg Eq/mL) and Na+/K+ ATPase (0.44 ± 0.03 and 0.42 ± 0.02 µg Eq/mL), compared to cancer control (69.68 ± 3.46 µg Eq/mL). In addition, both cancer biomarkers—i.e., prostate-specific antigen and carcinoembryonic antigen were significantly lowered as evidence of the ability of EBPS to protect and treat prostate cancer in chemically induced rats. EBPS showed protective and therapeutic efficacy on testosterone–DMBA-induced prostate cancer rats with a good safety margin. This study may go to clinical trials after a repeated study on another type of small experimental animal, their offspring, and one big experimental animal.

The Biochemical Effects of Silver Nanoparticles and Spirulina Extract on Experimentally Induced Prostatic Cancer in Rats

Prostate cancer (PCa) is the most diagnosed cancer in 112 countries and the second leading cause of death in men in 48 countries. We studied the outstanding agents silver nanoparticles (AgNPs) and Spirulina algae (Sp) for the management of PCa once as monotherapy or last as a combination. PCa in rats was induced using bicalutamide (Casodex®) and testosterone, followed by (7, 12-dimethylbenz[a]anthracene). Then, testosterone was injected s.c. for 3 months. Rats were divided into six groups, with 12 rats in each group. Group I was assigned as the control (co), group II as the PCa model, group III treated with AgNPs, group IV treated with Spirulina extract, group V treated with a combination of AgNPs plus Spirulina, and group VI treated with bicalutamide. The results show that AgNPs could normalize IL-6 levels and could overcome the hormonal disturbance induced in PCa rats along the hypothalamic–pituitary–testis axis. Spirulina revealed a significant reduction in the level of total and free prostatic specific antigen (PSA) to the same level as bicalutamide treatment, which was the same as the control group. Histopathological study revealed regression (75%) of the histological pattern of high-grade prostatic intraepithelial neoplasia (HGPIN) for Spirulina alone, and (50%) for bicalutamide. The best effect on IL-6 decline was reached with the AgNPs/Spirulina combination as well as bicalutamide treatment compared with the PCa group. Bicalutamide treatment significantly decreased the PSA concentration relative to the PCa group and reached the normal level. Adding Spirulina to AgNPs as a combination enhanced its effect on all mentioned drawbacks associated with PCa except hormonal imbalance that needs more adjustments.

Anticancer activity of Alpinia purpurata (Vieill) K. Schum. against MNU and testosterone induced prostate cancer in male Wistar albino rats

BackgroundNumerous Chinese herbal extracts have been proved to inhibit the development of prostate cancer. Zingiberaceae family is one type of plant used as an ingredient in traditional Chinese medicine (TCM). The genus Alpinia species of the Zingiberaceae family are well-known traditional herbal medicine for anti-inflammatory, antioxidant, antimicrobial, anti-dermatophytic, anti-nociceptive, hepatoprotective, immune stimulatory and anticancer activities. In vivo anticancer activity of Alpinia purpurata were studied in MNU and testosterone induced prostate cancer rats. MethodsThe induction of prostate cancer by using Wistar strain rats. The animals were divided into five groups. Group 1- Control, normal healthy rats Group 2- Rats were induced prostate cancer by daily intraperitoneal injection of testosterone (T) (100 mg/kg bw) in 0.3 ml propylene glycol for 3 days. One day after the testosterone injection, all the rats received intravenous injection of N-methyl N-nitrosourea (MNU) (50 mg/kg bw) (dissolved in saline at 10 mg/ml), through the tail vein for a period of one week. One week after MNU administration, rats received daily intraperitoneal injection of 2 mg/kg bw testosterone for 60 days. Group 3 - Rats were treated as group 2 along with Finasteride (25 mg/kg bw) supplemented throughout the entire experimental period of 2 months. Group 4 - Rats were treated as group 2 and simultaneously treated with daily dose of 200 mg/kg bw of the crude leaf ethyl acetate extract of Alpinia purpurata through oral gavage for 2 months. Group 5 - Rats were received daily dose of 200 mg/kg bw of crude, leaf ethyl acetate extract of Alpinia purpurata through oral gavage for 2 months. After the experimental period of 4 months, the animals were sacrificed by cervical dislocation under mild chloroform anesthesia. All biochemical parameters and histopathological studies were carried out. ResultsThe biochemical parameters such as total protein, enzymatic and non-enzymatic antioxidants and membrane bound enzymes were decreased whereas LPO, tumor markers, nucleic acid constituents were increased in prostate and seminal vesicle tissues of cancer induced group. The hematological, lipid parameters were altered and prostate markers, renal markers and liver markers were increased in serum. Those levels were brought back to near normal upon treatment with ethyl acetate leaf extract of Alpinia purpurata and standard drug finasteride. No significant changes were observed on treatment with plant extract alone group which indicated that there is no toxic substance present in Alpinia purpurata which was confirmed by the histopathological analysis of organs liver, kidney, prostate gland and seminal vesicle. ConclusionOn the basis of our findings, it is concluded that Alpinia purpurata might be used as an anticancer agent for the management of carcinoma in future.

Effects of green tea on prostate carcinogenesis in rat models and a human prostate cancer xenograft model.

There is evidence to suggest that green tea soy may have protective effects against prostate cancer, but there are several epidemiologic and clinical studies that did not identify such an effect. We tested the notion of protective effects in a rat model of prostate carcinogenesis that has been predictive of the effects of selenium and vitamin E in randomized clinical trials and a human prostate cancer xenograft model in nude mice and rat prostate tumor cells transplanted in immune-competent syngeneic animals. Prostate cancer was induced in rats with methylnitrosourea and testosterone and tumor incidence was determined. Subcutaneous tumor growth was measured resulting from injected cells isolated from rat prostate cancers grafted in syngeneic animals and from the prostate-specific antigen (PSA)-producing human prostate cancer PC346 xenografted in nude mice. Brewed decaffeinated green tea infusion or caffeinated green tea extract and the same 300 mg/ml concentration of caffeine were provided in drinking water of the rats and nude mice. Caffeinated green tea extract and caffeine provided in drinking water did not modify the induction of prostate cancer in the rat model compared with control rats. The same drinking water treatments also did not affect the growth and PSA production of PC346 human prostate cancer xenografts in nude mice and the growth of two transplantable rat prostate cancer tumor lines in Wistar Firth rats. Brewed green tea infusion as drinking water did also not affect tumor growth in these xeno- and allograft models. These animal studies with drinking water exposure to green tea and caffeine do not support the idea that green tea is protective against prostate cancer.

The Possible Protective and Therapeutic Role of Aqueous Extract of Avocado Seeds on Experimentally Induced Prostate Cancer in Adult Male Albino Rats

The Possible Protective and Therapeutic Role of Aqueous Extract of Avocado Seeds on Experimentally Induced Prostate Cancer in Adult Male Albino Rats

English

Prostate cancer is the leading cause of mortality in men worldwide, and dietary fat influence its incidence. This study investigated the effect of feeding Tetracarpidium conophorum seed oil (TCSO) on 3-methylcholanthrene (MCA) induced prostate cancer in Wistar rats, the expression of cyclooxygenase-2 (COX-2) and peroxisome proliferator activated receptor gamma (PPAR-?) in the prostatic tissues. The TCSO was extracted with n-hexane in a Soxhlet apparatus and characterized by gas chromatography. Forty-eight male wistar rats (4 weeks old) were divided into three groups of 16 rats each and fed for 12 weeks. Group A and B animals were fed with diet containing TCSO extract. The animals in Groups A and C received intraperitoneally a dose of MCA (150 mg/kg) after 30 days of feeding. Groups A and B rats were fed with diet containing 10% of extracted TCSO throughout the period of the experiment. Results showed that COX-2 activity significantly decreased (p &lt; 0.05) in Group A (0.71&plusmn;0.07) and B (0.60&plusmn;0.05) when compared with Group C (1.17&plusmn;0.10) with increased COX-2 expression. PPAR-gamma activity was significantly increased (p &lt; 0.05) in Group A (1.89&plusmn;0.13) and B (2.30&plusmn;0.15) in comparison with Group C (1.16&plusmn;0.10) which has the lowest PPAR-gamma expression. TCSO extract delayed latency period in Group A where lumps were observed after 4 weeks of 3-methylcholanthrene induction in comparison with Group C where lumps were observed in less than 2 weeks of MCA induction. Gamma-linoleic acid, docosahexaenoic acid and myristoleic acid were higher in the liver cell membrane of animals in Group A compared to animals in Group C. This work therefore showed that TCSO contains bioactive components that may oppose prostate carcinogenesis induced by MCA. Key words: Cyclooxygenase-2, linoleic acid, prostate cancer, Tetracarpidium conophorum, polyunsaturated fatty acid.

SIROF stabilized PEDOT/PSS allows biocompatible and reversible direct current stimulation capable of driving electrotaxis in cells

Electrotaxis is a naturally occurring phenomenon in which ionic gradients dictate the directed migration of cells involved in different biological processes such as wound healing, embryonic development, or cancer metastasis. To investigate these processes, direct current (DC) has been used to generate electric fields capable of eliciting an electrotactic response in cells. However, the need for metallic electrodes to deliver said currents has hindered electrotaxis research and the application of DC stimulation as medical therapy. This study aimed to investigate the capability of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) on sputtered iridium oxide film (SIROF) electrodes to generate stable direct currents. The electrochemical properties of PEDOT/PSS allow ions to be released and reabsorbed depending on the polarity of the current flow. SIROF stabilized PEDOT/PSS electrodes demonstrated exceptional stability in voltage and current controlled DC stimulation for periods of up to 12 hours. These electrodes were capable of directing cell migration of the rat prostate cancer cell line MAT-LyLu in a microfluidic chamber without the need for chemical buffers. This material combination shows excellent promise for accelerating electrotaxis research and facilitating the translation of DC stimulation to medical applications thanks to its biocompatibility, ionic charge injection mechanisms, and recharging capabilities in a biological environment.

Peptide based nano-drug candidate for cancer treatment: Preparation, characterization, in vitro and in silico evaluation

Tyrosyllysylthreonine (YKT) tripeptide has antibacterial, antiviral, anticancer and antioxidant properties based on the properties of the amino acids Tyrosine, Lysine and Threonine in its structure. The aim of this study is to design a peptide-based nano-drug candidate and to increase the effectiveness of the tripeptide and prevent its adverse effects. In this purpose, YKT loaded chitosan nanoparticles (CNPs) were synthesized by using a modified version of the ionic gelation method. The nanoparticles were characterized with various techniques such as Dynamic Light Scattering (DLS), UV–Vis, FTIR-ATR. Besides, scanning electron microscopy (SEM) was used to investigate the morphology of the nanoparticles. In addition, the in vitro cytotoxicity of YKT peptide and YKT loaded CNPs were comparatively examined on the Rat prostate cancer (MAT-Lylu) cell line. Moreover, in silico studies were conducted via theoretical methods such as MD, Molecular docking and ADME (Absorption, Distribution, Metabolism and Excretion) analysis. In conclusion, in vitro cell culture and in silico molecular docking studies were performed for YKT loaded CNPs in order to contribute to design of peptide based controlled release system for use in cancer therapy. It was discussed whether YKT loaded CNPs may use as nano-drug for prostate cancer treatment.

High-grade tumours promote growth of other less-malignant tumours in the same prostate.

Prostate cancer is a multifocal disease, but if and how individual prostate tumours influence each other is largely unknown. We therefore explored signs of direct or indirect tumour–tumour interactions in experimental models and patient samples. Low‐metastatic AT1 and high‐metastatic MatLyLu (MLL) Dunning rat prostate cancer cells were injected into separate lobes of the ventral prostate of immunocompetent rats. AT1 tumours growing in the same prostate as MLL tumours had increased tumour size and proliferation compared to AT1 tumours growing alone. In addition, the vasculature and macrophage density surrounding the AT1 tumours were increased by MLL tumour closeness. In patient prostatectomy samples, selected to contain an index tumour [tumour with the highest grade, International Society of Urological Pathology (ISUP) grade 1, 2, 3 or 4] and a low‐grade satellite tumour (ISUP grade 1), cell proliferation in low‐grade satellite tumours gradually increased with increasing histological grade of the index tumour. The density of blood vessels and CD68+ macrophages also increased around the low‐grade satellite tumour if a high‐grade index tumour was present. This suggests that high‐grade tumours, by changing the prostate microenvironment, may increase the aggressiveness of low‐grade lesions in the organ. Future studies are needed to explore the mechanisms behind tumour–tumour interactions and their clinical importance. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Functional Impact of Acidosis-Regulated MicroRNAs on the Migration and Adhesion of Tumor Cells.

Tumor tissue shows special features in metabolism in contrast to healthy tissue. Besides a distinctive oxygen deficiency, tumors often show a reduced extracellular pH (acidosis) resulting from an intensified glycolysis not only under hypoxic but also under normoxic conditions (Warburg effect). As shown in previous studies, cell migration is increased in AT1 prostate carcinoma cells after incubation at pH6.6, and this leads to an increased number of lung metastases in vivo. However, the signaling pathway causing these functional changes is still unknown. Possible mediators could be acidosis-regulated microRNAs (miR-7, miR-183, miR-203, miR-215). The aim of the study was therefore to analyze whether a change in the expression of these microRNAs has an impact on the tumor cell migration and adhesion. Studies were performed with AT1 rat prostate cancer cells which were incubated for 24h at pH7.4 or 6.6. Keeping AT1 tumor cells at low pH increased the migratory capacity by about 100%. But also the decrease of miR-203 and miR-215 expression (at normal pH) led to an increase in migration velocity by 50%. In contrast, cell adhesion was increased by about 75% at low pH. However, an increase in miR-215 expression at pH6.6 reduced the adhesion by trend. These results clearly indicated that the extracellular pH has an impact on migration and adhesion of tumor cells. In this mechanism, pH-regulated microRNAs could play a role since changes in the expression of these microRNAs (especially miR-203) are also able to modulate the migratory behavior.