Human Prostate Adenocarcinoma Cell Research Articles

Azolato-Bridged Dinuclear Platinum(II) Complexes Exhibit Androgen Receptor-Mediated Anti-Prostate Cancer Activity.

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Targeting GLI1 and BAX by nanonoscapine could impede prostate adenocarcinoma progression

Prostate cancer as a critical global health issue, requires the exploration of a novel therapeutic approach. Noscapine, an opium-derived phthalide isoquinoline alkaloid, has shown promise in cancer treatment thanks to its anti-tumorigenic properties. However, limitations such as low bioavailability and potential side effects have hindered its clinical application. This study introduces nanonoscapine as a novel medication to overcome these challenges, leveraging the advantages of improved drug delivery and efficacy achieved in nanotechnology. We monitored the effects of nanonoscapine on the androgen-sensitive human prostate adenocarcinoma cell line, LNCaP, investigating its impact on GLI1 and BAX genes’ expressions, crucial regulators of cell cycle and apoptosis. Our findings, from MTT assays, flow cytometry, and gene expression analyses, have demonstrated that nanonoscapine effectively inhibits prostate cancer cell proliferation by inducing G2/M phase arrest and apoptosis. Furthermore, through bioinformatics and computational analyses, we have revealed the underlying molecular mechanisms, underscoring the therapeutic potential of nanonoscapine in enhancing patient outcomes. This study highlights the significance of nanonoscapine as an alternative or adjunct treatment to conventional chemotherapy, warranting further investigation in clinical settings.

Oligo cyc-DEP: On-chip cyclic immunofluorescence profiling of cell-derived nanoparticles.

We present a follow-on technique for the cyclic-immunofluorescence profiling of suspension particles isolated using dielectrophoresis. The original lab-on-chip technique ("cyc-DEP" [cyclic immunofluorescent imaging on dielectrophoretic chip]) was designed for the multiplex surveillance of circulating biomarkers. Nanoparticles were collected from low-volume liquid biopsies using microfluidic dielectrophoretic chip technology. Subsequent rounds of cyclic immunofluorescent labeling and quenching were imaged and quantified with a custom algorithm to detect multiple proteins. While cyc-DEP improved assay multiplicity, long runtimes threatened its clinical adoption. Here, we modify the original cyc-DEP platform to reduce assay runtimes. Nanoparticles were formulated from human prostate adenocarcinoma cells and collected using dielectrophoresis. Three proteins were labeled on-chip with a mixture of short oligonucleotide-conjugated antibodies. The sample was then incubated with complementary fluorophore-conjugated oligonucleotides, which were dehybridized using an ethylene carbonate buffer after each round of imaging. Oligonucleotide removal exhibited an average quenching efficiency of 98±3% (n=12 quenching events), matching the original cyc-DEP platform. The presented "oligo cyc-DEP" platform achieved clinically relevant sample-to-answer times, reducing the duration for three rounds of cyclic immunolabeling from approximately 20 to 6.5h-a 67% decrease attributed to rapid fluorophore removal and the consolidated co-incubation of antibodies.

Antiviral and cytotoxic activities and chemical profiles of two species of Abies nordmanniana from Türkiye.

Abies is an important genus of the family Pinaceae, with about 50 species found in the highlands of Asia, Europe, North Africa, and North and Central America. The principal aim of the present work was to investigate the chemical content and biological potential of the resin and cone from Abies nordmanniana subsp. bornmulleriana and Abies nordmanniana subsp. equi-trojani, respectively. The flavonoid and phenolic contents of the resin and cones were evaluated using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Additionally, the essential oil and fatty acid compositions were analyzed using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC-FID), respectively. Cytotoxicity of the extracts and essential oils were screened against certain cancer cell lines, namely, human prostate adenocarcinoma cell line (PC3), human lung adenocarcinoma cell line (A549), human pancreatic cancer cell line (PANC-1), human hepatocellular carcinoma cell line (HepG2), human breast cancer cell line (MDA-MB231), and normal human lung fibroblast cell line (CCD-34-LU), with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. According to the MTT results, hexane extracts of both cone (CH) and resin (RH), ethanol-water (CEW), dichloromethane (CD), and acetone (CA) extracts of the cone mostly inflict cytotoxicity in HepG2 cell line. Antiviral activities of Abies nordmanniana subsp. extracts at doses of 5 μg/g and 10 μg/g were also evaluated in ovo for their virucidal activity against avian coronavirus. Abies nordmanniana subsp. extracts exhibited concentration-dependent antiviral activity on specific pathogen-free embryonated chicken eggs. Significantly, cone acetone extract (CA), cone ethanol extract (CE), and cone dichloromethane extract (CD) of Abies nordmanniana subsp. exhibited strong inhibition of the virus at a concentration of 10 μg/g. The most potent virucidal activity was observed with ethanol-water extract of conifer form (CEW). According to these results, it was proved that Abies nordmanniana species could be a potential, sustainable, and renewable drug source, especially considering the impressive antiviral and significant cytotoxic activity potentials.

Effects of p300 inhibition on prostate cancer cell growth

Background: Radiation is a central component of many anti-cancer therapy regimens, utilized for more than half of all cancer patients. Despite advances in the delivery and success of radiation treatment, many individuals express, or will develop, radioresistance, a major contributor to treatment failure and malignant progression. While the etiology of radioresistance is complex, it may be mediated in part by expression of p300, a histone acetyltransferase known to facilitate DNA repair. We hypothesized that inhibition of p300 would increase radiosensitivity of prostate cancer cells in vitro. Methods: Human prostate adenocarcinoma (PC-3) cells were grown in tissue culture flasks incubated at 37° C with 5% CO2. Cells were randomized to receive 1 μM CCS 1477, a selective inhibitor of p300, or vehicle for 1 hour prior to a single treatment of 0 Gy (NR+ or NR-, respectively) or 2 Gy radiation (R+ or R-, respectively). Four hours after radiation, cells were seeded into 100 mm diameter tissue culture dishes and incubated for 10 days. Cells were then stained, and colonies > 50 cells were counted to determine clonogenic survival. Cell survival was corrected for plating effciency and group comparisons were made using a two-way ANOVA. Results: Results were determined from the average of 3 separate experiments. Compared to non-radiated controls (NR-), survival of R- was reduced to 47%, while survival of R+ was reduced to 32%. However, there was no significant difference between % survival of R- and R+. Conclusions: In vitro, 1 μM exposure to CCS 1477 does not reduce clonogenic survival in PC-3 cells subjected to 2 Gy radiation. The duration of exposure and concentration of CCS 1477 may not be adequate to elicit significant improvements in radiosensitivity of PC-3 cells to 2 Gy radiation. Future experiments will explore the effects of varying durations of exposure and concentrations of CCS 1477. Additionally, it remains to be determined whether CCS 1477 improves radiosensitivity in other cancer cell lines (e.g., breast cancer). Johnson Cancer Research Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Facile and Eco-Friendly Synthesis of Silver Nanoparticles using Semecarpus anacardium and their Antibacterial and Anticancer Activity

Plant extracts are utilized to synthesize nanoparticles containing bioactive compounds that can effectively decrease metal toxicity. In present study, the aqueous extracts of Semecarpus anacardium leaves and stems were used to reduce silver nitrate and synthesize silver nanoparticles (AgNPs), which have potent antibacterial and anticancer effects. The physico-chemical methods such as XRD, UV-Vis, Fourier transform IR and SEM were used to characterize the biogenci silver nanoparticles. These methods validated the synthesis of AgNPs with smaller size and homogeneously sphere-shaped AgNPs (10-50 nm) after incubation with S. anacardium leaf and stem extract. Stem extract derived AgNPs showed the significant cancer fighting abilities in the human breast (MDA-MB-231) and prostate adenocarcinoma (PC-3) cells compared to that of derived AgNPs. Stem extract derived AgNPs exhibits the significant antibacterial activity against E. coli and B. subtilis with respect to the gentamycin. Additionally, the study demonstrated that green synthetic AgNPs may be investigated for use as a treatment against bacterial infections.

Access to 8-Aminoindolizine Fused with Quinone via Cu(OAc)2-Catalyzed Domino [4+2] Annulation

AbstractCu(OAc)2-catalyzed [4+2] annulation of N-substituted pyrrole-2-carbonitriles with quinones allowed access to a wide range of 8-aminoindolizines fused with quinones through a domino process involving a sequence of intermolecular Michael addition, Thorpe–Ziegler type cyclization, and aromatization. Biological evaluation of the resulting quinone-8-aminoindolizine hybrids revealed significant anticancer effects of these compounds in human hepatocellular cells (HepG2) and prostate adenocarcinoma cells (PC-3).

A bis-quinoline ruthenium(II) arene complex with submicromolar cytotoxicity in castration-resistant prostate cancer cells.

A new Ru(II) arene chlorido organometallic complex [(η6-p-cymene)(L)RuCl]PF6 (named as pCYRuL) using 2-bis(quinolin-2-ylmethylene) hydrazine (L) was developed that exhibits potent anticancer activity against castration-resistant prostate cancer (CRPC) (IC50 = 0.71 μM), and it is 45 times more effective than the standard drug cisplatin (IC50 = 31.3 μM) in a castration-resistant human prostatic adenocarcinoma cell line (PC-3) but non-toxic in normal human kidney cells (HK2) as well as normal breast cells (MCF10A) and found that pCYRuL exerted anticancer activity via apoptosis induction and cell cycle arrest in the G2/M phase of PC-3 cells.

Chemical composition, antioxidant, antimicrobial and antiproliferative activities of the leaf essential oil of Roxburgh’s Cherry (Eugenia roxburghii), an underutilized species

Eugenia roxburghii (Myrtaceae), known as Roxburgh’s Cherry, is a wild edible fruit-producing plant having multiple use in traditional and folk medicines in India and Sri Lanka. In spite of its nutritional and medicinal importance, there is no report on the chemical composition and bioactivities of the essential oil (EO) of this species. In this article, the chemical composition of the leaf EO of E. roxburghii has been reported for the first time along with its antioxidant, antimicrobial and antiproliferative activities. GC–MS analysis of EO led to the identification of 41 compounds with β-caryophyllene (22.32%) as the major constituent. The EO exhibited strong antioxidant capacity in DPPH and ABTS assays with IC50 values of 15.12 ± 0.23 μg/mL and 7.32 ± 0.05 μg/mL, respectively. It also exhibited strong reducing power ability (EC50 = 1.47 ± 0.06 μg/mL). The EO showed highest sensitivity against enteric pathogenic bacteria, Shigella flexneri (ZOI = 24 ± 0.4 mm, MIC = 31.25 μg/mL) validating its ethnomedicinal claim against dysentery. Further, E. roxburghii EO showed significant antiproliferative activity against human colon (HCT-116, IC50 = 64.84 μg/mL) and prostatic adenocarcinoma (PC-3, IC50=70.11 μg/mL) cell lines. The present study suggests that EO can be used as an antiproliferative agent and for the treatment of enteric diseases.

Synthesis and biological evaluation of novel salicylidene uracils: Cytotoxic activity on human cancer cell lines and inhibitory action on enzymatic activity.

A series of salicylidene uracil (1-18) derived from 5-aminouracil and substituted salicylaldehydes were analyzed for cytotoxic activity and enzyme inhibitory potency. Nine out of eighteen derivatives (6-8, 10, 12-15, 18) are novel molecules synthesized for the first time in this work, and other derivatives were previously synthesized by our group. The compounds were characterized by Proton nuclear magnetic resonance, carbon nuclear magnetic resonance, fourier transform infrared spectroscopy, and elemental analysis. All compounds were tested for their in vitro cytotoxicity against PC-3 (human prostate adenocarcinoma), A549 (human alveolar adenocarcinoma), and SHSY-5Y (human neuroblastoma) cancer cell lines and the nontumorigenic HEK293 (human embryonic kidney cells) cell line. The 3,5-di-tert-butylsalicylaldehyde derived compound (8) was toxic to PC-3 human prostate adenocarcinoma cells, showing a promising IC50 value at 7.05 ± 0.76 μM. The present study also aimed to evaluate the inhibitory effects of the compounds against several key enzymes, namely carbonic anhydrase I and II (CA I and CA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione reductase (GR), which are implicated in various global disorders, such as Alzheimer's disease, epilepsy, cancer, malaria, diabetes, and glaucoma. The inhibitory profiles of the tested compounds were assessed by determining their Ki values, which ranged from 2.96 to 9.24 nM for AChE, 3.78 to 12.57 nM for BChE, 8.42 to 25.74 nM for CA I, 7.24 to 19.74 nM for CA II, and 0.541 to 1.124 μM for GR. Molecular docking studies were also performed for all compounds. Most derivatives exhibited much more effective inhibitory action compared with clinically used standards. Thus, our findings indicate that the salicylidene derivatives presented in this study are promising drug candidates that need further evaluation.

A Pharmacological Investigation of Eph-Ephrin Antagonism in Prostate Cancer: UniPR1331 Efficacy Evidence.

The Eph kinases are the largest receptor tyrosine kinases (RTKs) family in humans. PC3 human prostate adenocarcinoma cells are a well-established model for studying Eph-ephrin pharmacology as they naturally express a high level of EphA2, a promising target for new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth in prostate orthotopic murine models, but reduced distal metastasis formation. In order to improve the comprehension of the pharmacological targeting of Eph receptors in prostate cancer, in the present work, we investigated the efficacy of Eph antagonism both in vitro and in vivo, using UniPR1331, a small orally bioavailable Eph-ephrin interaction inhibitor. UniPR1331 was able to inhibit PC3 cells' growth in vitro in a dose-dependent manner, affecting the cell cycle and inducing apoptosis. Moreover, UniPR1331 promoted the PC3 epithelial phenotype, downregulating epithelial mesenchymal transition (EMT) markers. As a consequence, UniPR1331 reduced in vitro PC3 migration, invasion, and vasculomimicry capabilities. The antitumor activity of UniPR1331 was confirmed in vivo when administered alone or in combination with cytotoxic drugs in PC3-xenograft mice. Our results demonstrated that Eph antagonism is a promising strategy for inhibiting prostate cancer growth, especially in combination with cytotoxic drugs.

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.

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.

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.

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).

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.

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.