Human Prostate Adenocarcinoma Research Articles

Green Synthesis of Biocompatible Hybrid Ginger/Chitosan Carbon Nanodot Exhibiting Antiproliferative Activity on Carcinoma Cells

Carbon Nanodots (CDs)-modified chitosan and ginger (ginger/chitosan@CD) based biocompatible substrate was built with the purpose of assessing antiproliferation effect on prostate cancer cell line (PC-3), human prostate adenocarcinoma cell line (LNCaP), and breast cancer cell line (MCF-7). CDs were fabricated through a solvothermal synhesis process, and characterized with TEM, SERS, and UV-vis spectroscopy. In this study, the cytotoxic impact of ginger/chitosan CD, which was synthesized for the first time, was evaluated as a function of both dose (maximum concentration 500 μg/mL) and time (in 24 and 48 hours) in cancer cell lines by XTT assay. After 48 hours, the ginger/chitosan@CD combination was found to have a 50% inhibitory concentration (IC50) of 178.08 μg/mL in the PC-3 cell line, 246.44 μg/mL in the LNCaP prostate cancer cells, and 345.74 μg/mL in the MCF-7. Cancer cell proliferation was efficiently suppressed by the ginger/chitosan@CDs.

Green synthesis of titanium nanoparticles using a sustainable microalgal metabolite solution for potential biotechnological activities

AbstractIn this study, green synthesis of titanium nanoparticles using liquids metabolites of microalgae, Porphyridium cruentum, was performed to evaluate potential biotechnological activity. The rising rates of multidrug‐resistant bacteria and the number of cancer patients are driving the search for novel antimicrobial and anticancer agents to combat this threat. In recent years, with the increasing number of studies, nanomaterials are starting to be better understood and are emerging as a solution to this problem. Especially, green synthesized nanoparticles with anticancer, antioxidant, and antimicrobial activities have potential in biomedical applications because of their eco‐friendly and biocompatible nature. Scanning electron microscopy (SEM) images revealed that spherical shaped Ti‐NPs' size ranged from 62 to 133 nm. This study aimed to assess the effectiveness of antibacterial activity of Ti‐NPs and chitosan‐coated Ti‐NPs against Escherichia coli and Staphylococcus aureus using disc diffusion assay. It demonstrated the concentration‐dependent cytotoxic effect of Ti‐NPs of human prostate adenocarcinoma (PC‐3), human alveolar adenocarcinoma (A549), and human mammary gland adenocarcinoma (MDA‐MB) cancer cell lines. This present study shows promising outcomes for possible future applications of synthesized Ti‐NPs as a novel antibacterial and cytotoxic agent for biomedical applications such as drug delivery, biosensor, and hyperthermia.

3,5,7-trihydroxyflavone restricts proliferation of androgen-independent human prostate adenocarcinoma cells by inducing ROS-mediated apoptosis and reducestumour growth.

Flavonoids are among the largest groups of secondary metabolites. Studies suggestthat dietary intake of flavonoids reducesthe risk of cancer. 3,5,7-trihydroxyflavone (THF) belongs to the flavone class of flavonoids and potentially inhibits the growth of many cancers; however, it is unexplored in prostate cancer. This study reports the antiproliferative potential of THF in prostate cancer cell line via reactive oxygen species (ROS)-mediated cascades and examines the tumour reduction potential in swiss albino mice. The potency of THF was evaluated by employing cytotoxicity assays and wound healing assays. Cell cycle, ROS, mitochondrial membrane potential (MMP), and Annexin-V-FITC assay were performed using a flow cytometer. In vivo, anticancer potential was achieved using the mice Ehrlich Ascites Carcinoma (EAC) model. THF inhibits cell growth with IC50 of 64.30 µM (MTT), 81.22 µM (NRU) and 25.81 µM (SRB), substantiated by cell migration assay. Cell-cycle analysis revealed that THF increases the subdiploid population. Furthermore, the Annexin-V-FITC assay evoked a significant induction of late apoptosis at a higher concentration of THF. THF also disrupts MMP, caused by an increased generation of ROS. In the EAC model, THF significantly inhibits tumour growth and increases the percent survival of mice and ROS levels in EAC cells. Hence, it may be concluded that THF might execute its antiproliferative effect via inducing ROS generation and could be a promising lead for preclinical and clinical validations.

Volatile profiling coupled with multivariate analysis, antiproliferative and anti-inflammatory activities of rhizome essential oil of four Hedychium species from India

Ethnopharmacological relevanceThe genus Hedychium of family Zingiberaceae comprises several perennial rhizomatous species widely used in perfumery and traditional folk medicine to treat diseases related to asthma, diarrhoea, nausea, stomach disorders, inflammation and tumours. Several species of Hedychium have remained under-explored with respect to their chemical composition and biological activities. Aim of the studyThe current research aimed to explore the chemical composition and evaluate the antiproliferative and anti-inflammatory activities of rhizome essential oil from four Hedychium species (H. coccineum, H. gardnerianum, H. greenii and H. griffithianum). Materials and methodsCompound identification was accomplished using a Clarus 580 gas chromatography system in conjunction with mass spectrometry (GC-MS). The multivariate data statistics using chemometrics (PCA, PLS-DA, sPLS-DA) and cluster analysis (Dendrogram, Heat maps, K-means) were used to compare the similarity and relationship among Hedychium metabolomes. MTT assay was employed to visualize the antiproliferative property against MCF7, HepG2 and PC3 cancerous cell lines. The toxicity of essential oils was determined using 3T3-L1 non-tumorigenic/normal cells. Lipopolysaccharide (LPS)-induced RAW 264.7 cells were used to investigate the anti-inflammatory properties of Hedychium essential oils by measuring the production of nitric oxide (NO) using the Griess reagent method. Furthermore, the levels of prostaglandin (PGE2) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) was assessed using the ELISA technique. ResultsIn total, 82 compounds were identified in four targeted species of Hedychium from which 1,8-cineole (52.71%), β-pinene (32.83%), α-pinene (19.62%), humulene epoxide II (19.86%) and humulene epoxide I (19.10%) were the major constituents. Monoterpenes (8.5–59.9%) and sesquiterpenes (2.87–54.11%) were the two class of compounds, found as the most prevalent in the extracted essential oils. The multivariate analysis classified the four Hedychium species into three different clusters. Hedychium essential oils exhibited potent antiproliferative activity against MCF7, HepG2 and PC3 cancer cell lines with IC50 values less than 150 μg/mL where H. gardnerianum exhibited the highest selective cytotoxicity against human breast and prostate adenocarcinoma cells with an IC50 value of 44.04 ± 1.07 μg/mL and 56.11 ± 1.44 μg/mL, respectively. The essential oils on normal (3T3-L1) cells displayed no toxicity with higher IC50 values thereby concluding as safe to use for normal human health without causing any side effects. Besides, the essential oils at 100 μg/mL concentration revealed remarkable anti-inflammatory activity in LPS-activated RAW 264.7 murine macrophages by inhibiting the production of inflammatory mediators, with H. greenii exhibiting the maximum anti-inflammation response by significantly suppressing the levels of NO (84%), PGE2 (87%), TNF-α (94.3%), IL-6 (95%) and IL-1β (85%) as compared to LPS treated group. ConclusionThe present findings revealed that the Hedychium species traditionally used in therapeutics could be a potential source of active compounds with antiproliferative and anti-inflammatory properties.

ZERDEÇALIN BİYOAKTİF BİLEŞİĞİ KURKUMİN, GEMSİTABİNİN PROSTAT KANSERİ HÜCRELERİNDEKİ ANTİ-MALİGNANT ÖZELLİĞİNİ GELİŞTİREBİLİR

Objective: The aim of this study was to investigate the possible synergistic effect of curcumin on the anticancer features of gemcitabine on prostate cancer cells. Material and Method: The human prostate adenocarcinoma cell line LNCaP was used in the studies. The effect of the co-administration of gemcitabine and curcumin on the viability of LNCaP cells was investigated by the WST-1 assay. Autophagy, ubiquitin-proteasome system (UPS), unfolded protein response (UPR) and cell death-associated proteins, androgenic signaling, proto-oncogenic, angiogenic and epithelial-mesenchymal transition (EMT) associated protein levels were investigated by immunoblotting studies. Result and Discussion: Our results showed that curcumin potentiated the anticancer effects of gemcitabine on LNCaP cells. Co-administration of curcumin and gemcitabine strengthened the suppressive effect of gemcitabine on cell viability. Moreover, co-administration modulated the autophagy, more strongly stimulated UPS and UPR, suppressed androgenic signaling, led to the activation of cell death-related poly [ADP-ribose] polymerase 1 (PARP-1) and caspase-3 and strongly suppressed the expression levels of proto-oncogenic c-Myc and angiogenic vascular endothelial growth factor-A (VEGF-A). In addition, it was determined that co-administration negatively regulated EMT by stimulating E-cadherin expression and suppressing N-cadherin level. These results suggest that the combined usage of gemcitabine and curcumin may offer a potent therapeutic approach to prostate cancer by enhancing the anticancer effects of gemcitabine.

Abstract PR007: ERG-driven luminal prostate cancers emerge from Ck5+/Nkx3.1+ basal cells

Abstract TMPRSS2-ERG translocations are initiating lesions in nearly 50% of human prostate adenocarcinomas, often in conjunction with PTEN loss. In mice, prostate-specific expression of ERG using a Probasin-Cre driver (Pb-Cre4) is sufficient to induce invasive Ck8+ luminal adenocarcinoma with high penetrance in the context of Pten loss. Because TMPRSS2 expression in the human prostate is androgen-regulated and thereby largely restricted to luminal epithelial cells, it has been assumed that luminal cells are the likely cell of origin for TMPRSS2-ERG positive prostate cancers. To gain further support for this hypothesis, we examined the early stages of luminal adenocarcinoma initiation in the Pb-Cre ERG/Pten model at a single cell level. To our surprise, we found a highly proliferative population of ERG+ Ck5+ (a putative basal marker) cells that are enriched at the invasive front in a background of more canonical ERG+/Ck8+/Ck5- luminal tumor cells. We next performed lineage tracing experiments using Ck5-, Ck8- as well as Nkx3.1-Cre drivers, introduced via viral injection or tamoxifen induction, which collectively support the hypothesis that ERG-driven tumors originate in a subset of basal cells defined by Ck5+/Nkx3.1+. This conclusion is further supported by orthotopic transplantation of freshly isolated primary mouse prostate basal (Cd49f high) or luminal (Cd24 high) cells showing that ERG+/Ck8+ tumors arise preferentially from basal cells following ex vivo ERG/Pten activation. Time course experiments in organoids and in vivo show that ERG promotes Ck8+ luminal differentiation from highly proliferative Ck5+ cells, progressing through a Ck5+/Ck8+ intermediate cell state. Collectively, these data implicate a tumor initiating cell population defined by a mix of basal (Ck5) and luminal (Nkx3.1) markers that, under the influence of ERG expression, can expand and invade while retaining full luminal differentiation potential. Our results also suggest that widely held assumptions regarding luminal-specific expression of canonical markers such as Nkx3.1 and Probasin may need revision. Citation Format: Weiran Feng, Erik Ladewig, Nazifa Salsabeel, Huiyong Zhao, Young Sun Lee, Anuradha Gopalan, Hanzhi Luo, Wenfei Kang, Ning Fan, Eric Rosiek, Ignas Masilionis, Katia Manova-Todorova, Ronan Chaligné, Elisa de Stanchina, Brett S. Carver, Yu Chen, Dong Gao, Christina S. Leslie, Charles L. Sawyers. ERG-driven luminal prostate cancers emerge from Ck5+/Nkx3.1+ basal cells [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR007.

Anticancer Activity of 3,5-Bis(dodecyloxy)Benzoate-PAMAM Conjugates with Indomethacin or Mefenamic Acid.

The synthesis of conjugates with nonsteroidal anti-inflammatory drugs could improve their activity with less toxicity and these compounds could be used for the treatment of cancer. The aim of the present investigation was the synthesis of 3,5-bis(dodecyloxy)benzoate - PAMAM conjugates with indomethacin and mefenamic acid to examine their anticancer activity. The anticancer activity was studied of the conjugates against six human cancer cells U- 251, PC-3, K-562, HCT-15, MCF-7, SKLU-1, and the COS-7 (as a control) cell lines. The conjugates with indomethacin and mefenamic acid were characterized by 1H, 13C NMR one- and twodimension spectroscopy. All the conjugates synthetized with indomethacin or mefenamic acid showed anticancer activity against all the human cancer cell lines. The first generation of indomethacin conjugates showed better activity against the PC-3 (human prostatic adenocarcinoma) cell line than the second generation. But the second generation with indomethacin showed better activity against PC-3 than the first generation. The second-generation conjugate with mefenamic acid had strong selectivity to PC-3 cells with an IC50 value of 10.23 ± 1.2 μM in vitro. In the paper, we report the synthesis and spectroscopic analyses of new indomethacin or mefenamic acid conjugates. The overall results showed that the conjugate of the second generation with mefenamic acid could be a potential nanocarrier for human prostatic adenocarcinoma cancer treatment, our research will be continued.

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer.

Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further understand the biological function of NUSAP1, we used affinity purification and mass spectrometry proteomic analysis to identify NUSAP1 interactors. We identified 85 unique proteins in the NUSAP1 interactome, including ILF2, DHX9, and other RNA-binding proteins. Using proteomic approaches, we uncovered a function for NUSAP1 in maintaining R-loops and in DNA damage response through its interaction with ILF2. Co-immunoprecipitation and colocalization using confocal microscopy verified the interactions of NUSAP1 with ILF2 and DHX9, and RNA/DNA hybrids. We showed that the microtubule and charged helical domains of NUSAP1 were necessary for the protein-protein interactions. Depletion of ILF2 alone further increased camptothecin-induced R-loop accumulation and DNA damage, and NUSAP1 depletion abolished this effect. In human prostate adenocarcinoma, NUSAP1 and ILF2 mRNA expression levels are positively correlated, elevated, and associated with poor clinical outcomes. Our study identifies a novel role for NUSAP1 in regulating R-loop formation and accumulation in response to DNA damage through its interactions with ILF2 and hence provides a potential therapeutic target.

Facile, Single-Step Synthesis of a Series of D-Ring Ethisterones Substituted with 1,4-1,2,3-Triazoles: Preliminary Evaluation of Cytotoxic Activities.

A series of new D-ring ethisterones substituted with 1,4-1,2,3-triazoles were obtained in a facile manner via click chemistry reactions. The new compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry, IR and unequivocally by single crystal X-ray diffraction studies for compound 1. The cytotoxic activity of these derivatives was tested against a series of human cancer cell lines including human glioblastoma (U-251), human prostatic adenocarcinoma (PC-3), human colorectal adenocarcinoma (HCT-15), human mammary adenocarcinoma (MCF-7), human chronic myelogenous leukemia (K562), and human lung adenocarcinoma (SKLU-1). Derivatives (3, X=Cl) and (5, X=I) showed promising cytotoxicity activities for leukemia adenocarcinoma (K562) and lung adenocarcinoma (SKLU). CI50% of K562: 11.72±0.9 μM (3) and 24.50±1.0 μM (5). CI50% of SKLU: 14.9±0.8 μM (3) and 46.0±2.8 μM (5). In addition, DNA docking simulations showed that all compounds interact with DNA through crosslink instrastrand p-alkyl-like interactions.

New sulfa drug derivatives and their zinc(II) complexes: synthesis, spectroscopic properties and in vitro cytotoxic activities

Synthesis of four sulfa drug derivatives (L1–L4 ) and Zn(II) complexes derived from sulfonamide group antibiotic substances was carried out using the hydrothermal technique (HT) and their structures of the obtained compounds were explained using elemental analysis (EA), FT-IR and NMR (1H- and 13C-). Cytotoxic activities of four novel sulfa drug based-Schiff base compounds and their Zn(II) complexes were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay using MCF-7 (human breast cancer), Caco-2 (human colorectal adenocarcinoma), A2780 (human ovarian cancer) and LNCaP (human prostate adenocarcinoma) cell lines. LogIC50 values of all obtained compounds were computed with the Graphpad Prism 6 program after 24 h of treatment for MCF-7, Caco-2, A2780 and LNCaP cells. Comet assay experiments were performed using LogIC50 concentrations of all compounds to determine DNA damage. Based on the data obtained, all compounds significantly decreased MCF-7, Caco-2, A2780 and LNCaP cell viability compared to the control groups (p < 0.05).

Hedychium spicatum rhizome essential oil induces apoptosis in human prostate adenocarcinoma PC-3 cells via mitochondrial stress and caspase activation

Hedychium spicatum is an essential oil bearing plant extensively used in the traditional system of medicine in several countries. Previous research has revealed H. spicatum essential oil (HSEO) to exhibit anti-tumor activity, although the mechanism of action is still unknown. Therefore, the current study was designed to carry out a comprehensive characterization of HSEO and evaluate the chemotherapeutic potential of HSEO against cancerous cells. The volatile constituents of HSEO was determined by one-dimensional gas chromatography with time-of-flight mass spectrometry (GC-TOFMS) and two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-TOFMS). In total, 193 phytocompounds could be detected, out of which 140 were identified for the first time. The major phytoconstituents detected by GCxGC-TOFMS were β-pinene (10.94%), eucalyptol (6.45%), sabinene (5.48%) and trans-isolimonene (5.00%). GCxGC-TOFMS analysis showed two and half fold increase in the constituents over GC-TOFMS due to better chromatographic separation of constituents in the 2nd dimensional column. HSEO was tested for in vitro cytotoxic activity against cancerous (PC-3, HCT-116 and A-549) and normal (3T3-L1) cell, with HSEO being most selective for prostate cancer cell (PC-3) over non-tumorigenic fibroblast (3T3-L1) cell. HSEO treatment inhibited the colony formation ability of PC-3 cells. HSEO treatment caused apoptotic cell death and cell cycle arrest at G2/M and S phase in PC-3 cells. HSEO induced apoptosis via intracellular ROS accumulation, mitochondria depolarization and increased caspase-3, 8, and 9 levels in PC-3 cells. Additionally, HSEO treatment led to a decrease of Bcl-2 and Bcl-xL and increase of Bax and Bak protein levels. Overall, results from this study highlighted the anticancer potential of H. spicatum essential oil, which could be considered as a new agent for treating prostate cancer.

Lemon gum: Non-toxic arabinogalactan isolated from Citrus × latifolia with antiproliferative property against human prostate adenocarcinoma cells

Lemon gum (LG) obtained from Citrus × latifolia in Brazil was isolated and characterized. In addition, gum biocompatibility was evaluated in vitro and in vivo by Galleria mellonella and mice model. The cytotoxicity against tumor cells was also evaluated. The ratio of arabinose:galactose: rhamnose:4-OMe-glucuronic acid was 1:0.65:0.06:0.15. Small traces of protein were detected, emphasizing the isolate purity. Molar mass was 8.08 × 105 g/mol, with three different degradation events. LG showed antiproliferative activity against human prostate adenocarcinoma cancer cells, with percentage superior to 50 %. In vivo toxicity models demonstrated that LG is biocompatible polymer, with little difference in the parameters compared to control group. These results demonstrate advance in the study of LG composition and toxicity, indicating a potential for several biomedical and biotechnological future applications.

Retracted: In Vivo Growth Inhibition of Human Caucasian Prostate Adenocarcinoma in Nude Mice Induced by Amygdalin with Metabolic Enzyme Combinations.

[This retracts the article DOI: 10.1155/2022/4767621.].

β-ionone Inhibits Epithelial-Mesenchymal Transition (EMT) in Prostate Cancer Cells by Negatively Regulating the Wnt/β-Catenin Pathway.

β-ionone is a terminal cyclic analog of beta-carotenoids widely found in plants. In recent years, accumulating evidence has shown that β-ionone exerts antitumor effects on various malignant tumors. However, limited studies have revealed the role of β-ionone in regulating the epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells. This study aimed to investigate the effect of β-ionone on the EMT process of PCa, focusing on Wnt/β-catenin signaling pathway. After exposure to β-ionone, cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the Brdu proliferation assay. The Transwell and wounding healing were used to investigate the migration and invasion abilities of PCa cells. Expression of proteins involved in the EMT process (E-cadherin, N-cadherin, vimentin) and proteins in the Wnt/β-catenin pathway (β-catenin, GSK3-β, and p-GSK3-β) were explored by western blotting. The effects of β-ionone on β-catenin degradation were explored by cycloheximide tracking assay and in vitro ubiquitination assay. Nude mouse xenograft model was served as the model system in vivo. The migration, invasion, and EMT process of PCa Human PC-3 prostate adenocarcinoma cells (PC3) and Human 22RV1 prostate adenocarcinoma cells (22RV1) cells were significantly inhibited after β-ionone treatment. In addition, β-ionone also inhibited the growth and EMT process of subcutaneous xenograft tumors in nude mice. The study also found that β-catenin, which promotes EMT, was downregulated after β-ionone treatment. Further mechanistic studies revealed that β-ionone inhibited the Wnt/β-catenin pathway by accelerating the ubiquitination and degradation of β-catenin in PCa, thus inhibiting the downstream migration, invasion, and EMT processes. These findings demonstrate that β-ionone may be a potential natural compound targeting the Wnt/β-catenin pathway for the treatment of PCa.

Antiproliferative Action of Methanolic Petiole Extract of Eichhornia Crassipes on Human Prostate Adenocarcinoma Cell Line: An In Vitro Study.

An increasing number of people are turning to herbal medicines in their search for innovative pharmaceuticals since they are effective treatments for a wide variety of conditions and traditional herbs are rich in bioactive chemicals. In this study, we looked at whether or not a petiole extract of Eichhornia crassipes preserved in methanol inhibited the proliferation of prostate cancer (PC3) cell lines. Lakes in Ezhikkara, Ernakulum, Kerala, were the source of E. crassipes. Soxhlet extraction was used to create the extract. 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cell viability of methanolic petiole extract at various concentrations. Mean and standard deviation was used to determine absorbance scores. Utilizing probit analysis, we determined the IC50 value. The descriptive statistics to measure the percent of viable cells along with the regression equation were calculated using SPSS. It has been shown that the methanol extract significantly impacted PC3 cell lines' capacity to survive. It was also determined that increasing the medication concentration resulted in a decrease in cell viability. The percentage of living cells was measured after being exposed to methanol extracts at concentrations of 12.5 μg/ml, 25 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml, and found to be 95.13, 85.88, 76.12, 64.33, and 53.62 percent, respectively. With IC50 values of 199.488 g/ml, it was shown that methanolic petiole extracts of E. crassipes are cytotoxic. Using probit analysis, we determined that the regression equation is y = -0.2051x + 90.915, with an R2 value of 0.893. As a result of its chemotherapeutic properties, the E. crassipes petiole extract has the potential to be employed in therapeutic applications, with the ultimate goal of bettering prostate cancer management practices and clinical results by drastically lowering cell viability. The study's results may pave the way for fresh chemotherapeutic approaches to be developed for the treatment of androgen-independent prostate cancer.

Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the most common histological subtype of prostate cancer. Post-treatment biochemical recurrence is a challenging issue. ATAD1 (ATPase Family AAA Domain Containing 1) plays a vital role in mitochondrial proteostasis and apoptosis activity, while its clinical value in PRAD and its impact on the tumor microenvironment (TME) remain unanswered. In this study, we aimed to investigate the clinical value and possible mechanisms of ATAD1 in PRAD via multi-omics analysis. Using cBioPortal, we confirmed that ATAD1 alteration was associated with gene expression and unfavorable DFS. Deep deletion predominantly occurred in PRAD. By integrating DriverDBv3 and GEPIA2, we noted ATAD1 downregulation in PRAD tissues compared to normal tissues, associated with unfavorable DFS in PRAD patients. DNA repair genes ATM, PARP1and BRCA2 had positive associations with ATAD1 expression. We found that the generalization value of ATAD1 could be applied to other cancers such as KIRC and UCEC. In addition, LinkedOmics identified that the functional involvement of ATAD1 participates in mitochondrial structure and cell cycle progression. Using TIMER analysis, we demonstrated that ATAD1 downregulation correlated with an immunosuppressive TME. Furthermore, we accessed a GSE55062 dataset on UALCAN and discovered the involvement of ERG-mediated transcriptional repression on ATAD1 downregulation. Cross-association screening of shATAD1 efficacy vs. altered mRNAs identified 190 perturbed mRNAs. Then, functional enrichment analysis using the Metascape omics tool recognized that shATAD1-perturbed mRNAs are primarily in charge of the activation of Wnt/β-catenin pathway and lipid metabolic processes. In conclusion, multi-omics results reveal that ATAD1 downregulation is a clinical biomarker for pathological diagnosis and prognosis for patients with PRAD. Reduced ATAD1 may be involved in the enhanced activity of mitochondria and cell cycle, as well as possibly shaping an immunosuppressive TME. ERG serves as an upstream transcriptional repressor of ATAD1. Downstream mechanisms of ATAD1 are involved in Wnt/β-catenin pathway and lipid metabolic processes.

Increased MYBL2 expression in aggressive hormone-sensitive prostate cancer.

Loss of the histone demethylase KDM5D (lysine-specific demethylase 5D) leads to in vitro resistance of prostate cancer cells to androgen deprivation therapy (ADT) with and without docetaxel. We aimed to define downstream drivers of the KDM5D effect. Using chromatin immunoprecipitation sequencing (ChIP-seq) of the LNCaP cell line (androgen-sensitive human prostate adenocarcinoma) with and without silenced KDM5D, MYBL2-binding sites were analyzed. Associations between MYBL2 mRNA expression and clinical outcomes were assessed in cohorts of men with localized and metastatic hormone-sensitive prostate cancer. In vitro assays with silencing and overexpression of MYBL2 and KDM5D in androgen receptor (AR)-positive hormone-sensitive prostate cancer cell lines, LNCaP and LAPC4, were used to assess their influence on cellular proliferation, apoptosis, and cell cycle distribution, as well as sensitivity to androgen deprivation, docetaxel, and cabazitaxel. We found that silencing KDM5D increased histone H3 lysine K4 (H3K4) trimethylation and increased MYBL2 expression. KDM5D and MYBL2 were negatively correlated with some but not all clinical samples. Higher MYBL2 expression was associated with a higher rate of relapse in localized disease and poorer overall survival in men with metastatic disease in the CHAARTED trial. Lower MYBL2 levels enhanced LNCaP and LAPC4 sensitivity to androgen deprivation and taxanes. In vitro, modifications of KDM5D and MYBL2 altered cell cycle distribution and apoptosis in a cell line-specific manner. These results show that the transcription factor MYBL2 impacts in vitro hormone-sensitive prostate cancer sensitivity to androgen deprivation and taxanes, and lower levels are associated with better clinical outcomes in men with hormone-sensitive prostate cancer.

Novel Ru(II)-bipyridine/phenanthroline-lapachol complexes as potential anti-cancer agents

For the first time, we herein report on the syntheses of two new Ru(II)/bipyridine/phenanthroline complexes containing lapachol as ligand: complex (1), [Ru (bipy)2(Lap)]PF6 and complex (2), [Ru(Lap)(phen)2]PF6, where bipy = 2,2′-bipyridine and ph en = 1,10-phenanthroline; Lap = lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione). The complexes were synthesized and characterized by elemental analyses, molar conductivity, mass spectrometry, ultraviolet-visible and infrared spectroscopies, nuclear magnetic resonance (1H, 13C), and single crystal X-ray diffraction, for complex (2). In addition, in vitro cytotoxicity was tested against six cancer cells: A549 (lung carcinoma); DU-145 (human prostate carcinoma); HepG2 (human hepatocellular carcinoma), PC-3 (human prostate adenocarcinoma); MDA-MB-231 (human breast adenocarcinoma); Caco-2 (human colorectal adenocarcinoma), and against two non-cancer cells, FGH (human gingival normal fibroblasts) and PNT-2 (prostate epithelial cells). Complex (1) was slightly more toxic and selective than complex (2) for all cell lines, except against the A549 cells, where (2) was more potent than complex (1). The complexes induced an increase in the reactive oxygen species, and the co-treatment with N-acetyl-L-cysteine remarkably suppressed the ROS generation and prevented the reduction of cell viability, suggesting that the cytotoxicity of the complexes is related to the ROS-mediated pathway. Further studies indicated that the complexes may bind to DNA via minor groove interaction. Our studies also revealed that free Lap induces gene mutations in Salmonella Typhimurium, nevertheless, the complexes demonstrated the absence of genotoxicity by the Ames test. The present study provides a relevant contribution to understanding the anti-cancer potential and genetic toxicological events of new ruthenium complexes containing the lapachol molecule as a ligand.

Formulation, characterization and cellular toxicity assessment of a novel bee-venom microsphere in prostate cancer treatment

Bee venom (B.V.) is a toxin produced naturally by honey bees with several toxic and therapeutic efficacies. It is used in the treatment of different cancer kinds like renal, hepatic, and prostate cancer. Due to its protein nature, it is degraded in the upper gastrointestinal tract. Colon-targeted drug delivery systems represent a useful tool to protect B.V. from degradation and can be administered orally instead of I.V. infusion and traditional bee stinging. In the present study, B.V. loaded enteric-coated cross-linked microspheres were prepared by emulsion cross-linking method. Percentage yield, entrapment efficiency %, swelling degree, and in-vitro release are evaluated for prepared microspheres. Free B.V., optimized microspheres formula (F3), and doxorubicin cytotoxic effects were tested by MTT assay. Results concluded that free B.V. was more effective against the growth of human prostate adenocarcinoma (PC3) cells followed by optimized microspheres than doxorubicin. But both free B.V. and doxorubicin have a cytotoxic effect on normal oral epithelial cells (OEC). According to flow cytometric analysis, the optimized microsphere formula induced apoptosis and reduced necrosis percent at IC50 concentration. Furthermore, microspheres did not affect the viability of OEC. These results revealed that microspheres have a degree of specificity for malignant cells. Therefore, it seems that this targeted formulation could be a good candidate for future clinical trials for cancer therapy.