Cancer LNCaP Cells Research Articles

Phytochemical Profile and Biological Activities of the Endemic Thymbra nabateorum Occurring in AlUla County, South-West Saudi Arabia

Thymbra nabateorum, a plant species from the Lamiaceae family, is endemic to the Nabatian region, which spans southern Jordan and northwestern Saudi Arabia. It is renowned for its traditional uses and rich phytochemical profile. This study aims to examine the phytochemical composition of T. nabateorum and evaluate its biological activities, including antioxidant capacity, cytotoxic effects on cancer cell lines, and enzyme inhibition relevant to diabetes and neurodegenerative diseases. The essential oil (EO) and methanol extract of T. nabateorum were analyzed using Gas Chromatography–Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC). Antioxidant activity was assessed using the DPPH radical scavenging assay. Cytotoxicity was evaluated against MDA-MB231 and LNCaP cancer cell lines using the MTT assay. Enzyme inhibition assays were conducted to determine the inhibitory effects on α-amylase, α-glucosidase, and butyrylcholinesterase. GC-MS analysis revealed thymol (82.30%) as the major component of the essential oil, while HPLC identified significant phenolic compounds in the methanol extract, including diosmin (118.75 mg/g) and hesperidin (22.18 mg/g). The DPPH assay demonstrated strong antioxidant activity, with the methanol extract showing an IC50 of 11.97 μg/mL for α-amylase and 31.99 μg/mL for α-glucosidase, indicating notable antidiabetic potential. Cytotoxicity tests revealed significant antiproliferative effects against both cancer cell lines, with lower IC50 values compared to standard treatments. T. nabateorum exhibits substantial antioxidant, cytotoxic, and enzyme inhibition activities, supporting its traditional medicinal uses. These findings provide a scientific basis for further research into its bioactive compounds and potential applications in modern pharmacology, particularly in developing natural therapeutic agents for oxidative stress-related diseases and cancer.

In vitro antimicrobial, anticancer and antioxidant activities and bioactive contents of endemic Acanthus dioscoridis L. var. dioscoridis flowers from Türkiye

A. dioscoridis is a member of the Acanthaceae family and is represented by approximately 30 species. In Türkiye, 8 species, 6 of which are endemic, are distributed in Eastern and Central Anatolia. In the presented study, the antimicrobial, antiradical, and anticancer properties of flower extracts of endemic A. dioscoridis L. var. dioscoridis were investigated for the first time. The antiradical activity and phytochemical contents of this plant were also investigated. According to our study results, endemic A. dioscoridis flowers extract show anticancer activity against MCF-7, HCT-116 and LNCaP cancer cell lines, high antiradical activity against ABTS radicals, and effective antimicrobial activity against some microorganism-caused infection in humans. In conclusion, this study can be the first report about the anticancer, antiradical, and antimicrobial properties of endemic A. dioscoridis L. var. dioscoridis flower extracts.

Caffeic acid phenethyl ester (CAPE) Chitosan capped ZnO nanoparticles: Preparation, characterization, and its potential for the treatment of prostate cancer

Caffeic acid phenethyl ester (CAPE) Chitosan capped ZnO nanoparticles: Preparation, characterization, and its potential for the treatment of prostate cancer

Cytotoxicity of Myrtenal on Different Human Cancer Cell Lines

Aim: Myrtenal (Myrt), a monoterpene found in essential oils of various plant species, such as Citrus aurantium, Citrus limon, Mentha japonica and Zingiber officinale roscoe. Preclinical studies have reported that Myrt induces apoptosis in various cancer models. This study aimed to investigate the effects of Myrt on cell viability in human prostate (LNCaP), colon (Caco-2), breast (MCF-7) and ovarian (A2780) cancer cell lines. Materials and Methods: A2780, LNCaP, MCF-7 and Caco-2 cell lines were used in this study. All cell lines were treated with 1, 5, 25, 50 and 100 μM concentrations of Myrt for 24 hours. Changes in cell viability were determined by the MTT assay. The inhibitory concentration 50 (IC50) and logIC50 values of Myrt in cell lines was calculated based on the cytotoxicity results. Results: Myrt concentrations applied to Caco-2, A2780, MCF-7 and LNCaP cancer cell lines for 24 hours significantly decreased cell viability (%) (p<0.05). Conclusion: In conclusion, this study shows that Myrt has potent cytotoxic and antiproliferative properties against human A2780, LNCaP, MCF-7 and Caco-2 cancer cell lines.

Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells.

Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer-DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.

Aridanin and oleanane-3- O-β-D-glucoside-2′-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells

Tetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines. Eight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed. Out of the eight (1-8) isolates from T. tetraptera only oleanane-3-O-β-D-glucoside-2'-acetamide and aridanin showed potent cell growth arrest with an estimated CC50 of 15, 23, 16 and 17, 26, 16μg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-β-D-glucoside-2'-acetamide and aridanin at 10μg/mL were noticed. Oleanane-3-O-β-D-glucoside-2'-acetamide and aridanin at 2.5 and 10μg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145cells and increased the adherence of DU145cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin β-1 (10μg/mL) and integrin β-4 (2.5μg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8-18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated. This study outlines for the first time, the anticancer ability of compounds oleanane-3-O-β-D-glucoside-2'-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action.

Development and characterisation of a novel inhibitory anti-GH monoclonal antibody.

Excess growth hormone (GH) has been implicated in multiple cancer types and there is increasing interest in the development of therapeutic inhibitors targeting GH-GH receptor (GHR) signalling. Here we describe a panel of anti-GH monoclonal antibodies (mAbs) generated using a hybridoma approach and identify two novel inhibitory mAbs (1-8-2 and 1-46-3) that neutralised GH signalling. mAbs 1-8-2 and 1-46-3 exhibited strong inhibitory activity against GH-dependent cell growth in a Ba/F3-GHR cell viability assay, with EC50 values of 1.00 ± 0.27 and 0.5 ± 0.1 µg/mL, respectively. Cross-reactivity with the human placental hormones, placental lactogen (PL) and placental GH, was observed by ELISA, but neither antibody cross-reacted with mouse GH or human prolactin (PRL). mAb 1-8-2 had a binding affinity for GH of KD 0.62 ± 0.5 nM, while mAb 1-46-3 had a KD of 2.68 ± 0.53 nM, as determined by bio-layer interferometry. mAb 1-46-3 inhibited GH-dependent signal transduction in T-47D and LNCaP cancer cell lines and reduced GH-dependent cell growth and migration in the breast cancer cell line T-47D. mAb 1-46-3 inhibited T-47D cell viability more effectively than the GHR antagonist B2036. In conclusion, we describe two novel inhibitory anti-GH mAbs and provide in vitro evidence supporting development of these entities as anti-cancer therapeutics.

Cytotoxic and Antimicrobial Secondary Metabolites from Penicillium hetheringtonii IMBC-NMTP04

Chemical investigation of the sesame-associated fungal strain Penicillium hetheringtonii IMBC-NMTP04 resulted in isolation of five compounds, penicitrinone A (1), dihydrocitrinin (2), janthinone (3), coniochaetone B (4), and 9-oxo-10(E),12(E)-octadecadienoic acid (5). Their chemical structures were elucidated by spectroscopic methods, including 1D and 2D NMR and mass spectra in comparison with the literature data. Compound 1 showed modest cytotoxicity toward LNCaP, HepG2, MCF-7, KB, SK-Mel-2, and HL-60 human cancer cell lines, with IC50 values ranging from 60.1 to 84.2 mM while 5 was cytotoxic toward only HL-60 cell line (IC50 = 71.6 mM). All the compounds significantly inhibited E. faecalis, S. enterica, and C. albicans growth, with MIC values ranging from 12.5 to 50.0 mM. Compounds 2, 4, and 5 suppressed the growth of B. cereus, while both 1 and 2 showed antimicrobial effect against E. coli, with the same MIC value of 200 mM. This is the first time to report the chemical constituents of Penicillium hetheringtonii and the antimicrobial effect of 2–4.

Synthesis and in vitro Anti-proliferative Activities on LNCaP, LS180 and MKN45 of Novel 20(R)-Panaxadiol Derivatives.

20(R)-PD, a tetracyclic triterpenoid, is a non-natural saponin present in the form of protopanaxadiol. Because of its essential biological activities, especially anti-tumor activity, structural modification of 20(R)-PD and the development of innovative and novel 20(R)-PD derivatives with better anti-tumor activity are increasingly relevant. 20(R)-Panaxadiol (20(R)-PD) can inhibit tumor proliferation. Three series of novel 20(R-PD derivatives were synthesized by modifying the A-ring. The objective of this work was to synthesize and evaluate the in vitro anti-proliferative activities of 20(R)- PD derivatives in LNCaP, LS180, and MKN45 cancer cells. Structural modifications were performed at the C-3 position and A-ring. The in vitro anti-proliferative activities of novel derivatives in LNCaP, LS180, and MKN45 cells were evaluated by the MTT assay. The effects of compounds 5 and C9 on apoptosis were determined by flow cytometry. Compounds 5, B2, C2, C4, C7, C8, C9, C10, and C11 exhibited good anti-proliferative activities in LNCaP, LS180, and MKN45 cells in vitro. The best anti-proliferative activity was observed for the C-series derivatives with the introduction of amino acids at the C-3 position. C9 exhibited good potent activity with an IC50 of 2.89 μM. Compound C9 is a potential candidate with potent anti-proliferative activity.

Bifunctional Magnetite–Gold Nanoparticles for Magneto-Mechanical Actuation and Cancer Cell Destruction

Magnetite–gold dumbbell nanoparticles are essential for biomedical applications due to the presence of two surfaces with different chemical natures and the potential combination of magnetic and plasmonic properties. Here, the remote actuation of Fe3O4-Au hybrid particles in a rotating (1 Hz, 7 mT), static (7 mT) or pulsed low-frequency (31 Hz, 175 mT, 30 s pulse/30 s pause) magnetic field was studied. The particles were synthesized by a high-temperature wet chemistry protocol and exhibited superparamagnetic properties with the saturation magnetization of 67.9 ± 3.0 Am2 kg−1. We showcased the nanoparticles’ controlled aggregation in chains (rotating/static magnetic field) in an aqueous solution and their disaggregation when the field was removed. The investigation of nanoparticle uptake by LNCaP and PC-3 cancer cells demonstrated that Fe3O4-Au hybrids mainly escaped endosomes and accumulated in the cytoplasm. A significant fraction of them still responded to a rotating magnetic field, forming short chains. The particles were not toxic to cells at concentrations up to 210 μg (Fe3O4) mL−1. However, cell viability decrease after incubation with the nanoparticles (≥70 μg mL−1) and exposure to a pulsed low-frequency magnetic field was found. We ascribe this effect to mechanically induced cell destruction. Overall, this makes Fe3O4-Au nanostructures promising candidates for intracellular actuation for future magneto-mechanical cancer therapies.

In vitro anticancer, antimicrobial and antiradical properties and bioactive compounds of endemic Wiedemannia orientalis Fisch. & Mey. flowers

W. orientalis is a one-year herbaceous plant, located in the Lamiaceae family, and is called Ballıbaba in Turkish. In the presented study, the antimicrobial and anticancer properties of flowers extracts of endemic W. orientalis were investigated for the first time. Also, it was investigated the antiradical activity and phytochemical contents of this plant extracts. According to our study results, endemic W. orientalis flowers extract show very high anticancer activity against MCF-7, HCT-116 and LNCaP cancer cell lines, high antiradical activity against ABTS radicals, and effective antimicrobial activity against some microorganism caused infection in humans. In conclusion, endemic W. orientalis can be used as an anticancer and antimicrobial agent and this plant can be the subject of further studies in the field of herbal medicine.

Phenolic Glycosides from the Leaves of Iodes cirrhosa Turcz. with Cytotoxic and Antimicrobial Effects.

In the present study, 14 phenolic glycosides, including one new neolignan glycoside, iodescirrhoside A (1), three new flavonol glycosides, iodescirrhosides B-D (2-4), and 10 known metabolites were obtained from the methanol extract of Iodes cirrhosa leaves. Structural elucidation was performed by interpretating the 1D- and 2D- NMR, HR-ESI-MS, and CD spectra in comparison with literature data. All compounds were noncytotoxic to LU-1, HepG2, MCF-7, SK-Mel-2, and LNCaP cancer cell lines. Compound 11 significantly inhibited the growth of E. faecalis. In contrast, weak inhibition was observed for 1-9 and 14 against E. faecalis, for 1, 6-8, and 11 against S. aureus, for 6 and 13 against B. cereus, and 2, 4, and 6-9 against C. albicans.

Abstract 3809: Adaptation of prostate cancer cell lines to tumor microenvironment culture conditions induces expression of androgen receptor splice variant 7 and contributes to drug resistance

Abstract The tumor microenvironment (TME) has several characteristics that distinguish it from normal tissue, including elevated interstitial fluid pressures and hypoxic environments. Both pressurized and hypoxic culture conditions can influence gene and protein expression of tumor cells which can result in tumor metastasis and drug resistance. Enzalutamide is effective in treating metastatic castration-resistant prostate cancer (mCRPC), but majority of patients eventually develop resistance to enzalutamide. One of the biomarkers of enzalutamide resistance is the expression of androgen receptor splice variant 7 (AR-V7), but the mechanism of how AR-V7 expression is upregulated in prostate cancer is unclear. To investigate the influence of TME culture conditions on prostate cancer cell lines, 22Rv1 and LNCaP cell lines were incubated under pressurized and hypoxic culture conditions (2 PSI + 1%O2) for a minimum of 7 days. We compared cell growth, morphology changes, gene expression profiles and drug response to enzalutamide treatment. The growth of 22Rv1 and LNCaP cells was markedly inhibited under TME culture conditions, accompanied by distinct changes in cell morphology. 22Rv1 and LNCaP cells cultured under TME conditions exhibited increased resistance to enzalutamide treatment. Higher levels of AR-V7 expression were detected in 22Rv1 and LNCaP cell lines maintained for 7 days in TME culture conditions. RNA-seq data identified 700+ genes that were differentially expressed in 22Rv1 and LNCaP cell lines adapted to TME culture conditions. GSEA analysis identified signaling pathways associated with hypoxia, glycolysis and epithelial-mesenchymal transition were upregulated under TME culture conditions, and the pathways of xenobiotic metabolism and oxidative phosphorylation were downregulated by TME culture conditions. In summary, adaptation to TME culture conditions can promote the expression of AR-V7 in prostate cancer cell lines and can contribute to enzalutamide drug resistance. Adaptation of cell lines to TME culture conditions can provide meaningful insights into mechanisms of drug resistance while providing a novel approach to identify targets and biomarkers of drug resistance. Citation Format: Yunmin Li, Albert Wong, Ann Lu, James Lim. Adaptation of prostate cancer cell lines to tumor microenvironment culture conditions induces expression of androgen receptor splice variant 7 and contributes to drug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3809.

Antioxidative, anti-inflammatory, and anticancer properties of the red biopigment extract from Monascus purpureus (MTCC 369).

In this study, the Monascus purpureus (MTCC 369) extracted biopigment produced by solid-state fermentation was evaluated for its therapeutic potential using human prostate LNCaP cells. Antioxidant efficacy of the red biopigment determined using 2,2 diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, and ferric reducing antioxidant power assays was found to be 53.16%, 86.27%, and 13.83%, respectively. In addition, expression studies of target gene superoxide dismutase 2 (SOD-2) showed that increasing concentrations (10-50 μg/ml) of the biopigment enhanced its expression from 0.91- to 1.905-fold. An inhibitory effect of 0.424-0.627-fold was observed in the expression of glutathione peroxidase (GPX) with a similar increase in biopigment concentration. Addition of quercetin (positive control) at 50 μg/ml led to 0.295-fold decrease in GPX expression. In contrast, the expression of SOD-2 increased by 1.026-fold in the presence of quercetin. The biopigment also showed an increased serological IL-10 expression (an anti-inflammatory agent) ranging from 1034.58 to 4657.89 pg/ml. Treatment of LNCaP cells with the red biopigment (10-100 μg/ml) resulted in significant (p < .05) reduction (upto 79.86%) in viability and 51.79%-89.86% reduction in cell metabolic activity. Fluorescent microscopy examination of red biopigment-treated cells showed significant inhibition of normal cellular morphology including condensed nuclei, membrane blebbing, and apoptotic bodies, thus confirming its cytotoxic potential. Results of this study revealed that the red biopigment has the potential to modulate the expression of antioxidative and anti-inflammatory markers in addition to being cytotoxic to the LNCaP cancer cells. PRACTICAL APPLICATIONS: These findings indicate that cell treatment with red biopigment has the potential to modulate anti-oxidative, pro-inflammatory and anti-inflammatory genes for therapeutic effects, which is further enhanced by its cytotoxic activity against cancer cells. Considering these cell-based observations, Monascus red biopigment has ample potential as a useful supplement to formulate therapeutic products that delay the development of inflammatory-related diseases and associated complications.

A new phenoxo-bridged dicopper Schiff base complex: Synthesis, crystal structure, DNA/BSA interaction, cytotoxicity assay and catecholase activity

A new pyridine-based Schiff base dicopper complex involving μ -phenoxo- μ 1,1 -nitrate bridging moiety was synthesized and characterized. DNA/BSA interactions of Cu II complex were investigated. MTT assay of the complex showed moderate toxicity against MCF-7, HeLa and LNCaP cancer cells. Furthermore, catecholase activity of the complex in MeCN and DMF showed high activity in catalyzing the oxidation of 3,5-DTBC to 3,5-DTBQ. The DNA/BSA interaction and catecholase activity of a new binuclear water-soluble Cu(II) complex [Cu II 2 L( μ 1,1 -NO 3 )( μ -OH)(NO 3 )(H 2 O)], where L = [2,6-bis{N-(2-pyridylethyl)formidoyl}-4-methylphenol] involving μ -phenoxo N 2 O 4 Schiff base ligand, have been studied. The complex interaction with FS-DNA/BSA was investigated by absorption and fluorescence titration, cyclic voltammetry, circular dichroism, agarose gel electrophoresis and viscosity measurements. The complex is characterized by elemental analysis, UV–vis and FT-IR spectroscopy. X-ray analysis revealed the dinuclear Cu(II) ions located in a six-coordinated distorted environment. Docking simulation analysis and competitive binding experiments with ethidium bromide showed the complex interaction with DNA mainly via intercalation mode with the K b value of 2.78 × 10 4 M −1 . Upon increasing DNA concentration, the fluorescence intensity of the complex enhanced about two folds, and a strong green fluorescence was observed via naked eyes, demonstrating the complex behaves like a “light switch” for DNA in water. Finally, cytotoxic activity was investigated by MTT assay against MCF-7, HeLa and LNCaP cancer cells.

Effect of Copper and Selenium Supplementation on the Level of Elements in Rats' Femurs under Neoplastic Conditions.

A study was conducted to determine the effect of long-term supplementation with selenium and copper, administered at twice the level used in the standard diet of rats, on the content of selected elements in the femoral bones of healthy rats and rats with implanted LNCaP cancer cells. After an adaptation period, the animals were randomly divided into two experimental groups. The rats in the experimental group were implanted with prostate cancer cells. The rats in the control group were kept in the same conditions as those in the experimental group and fed the same diet, but without implanted cancer cells. The cancer cells (LNCaP) were intraperitoneally implanted in the amount of 1 × 106 (in PBS 0.4 mL) at the age of 90 days. The content of elements in the samples was determined by a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In the femoral bones of rats with implanted LNCaP cells, in the case of the standard diet and the copper-enriched diet, there was a marked decreasing trend in the content of the analysed elements relative to the control rats. This may indicate slow osteolysis taking place in the bone tissue. Contrasting results were obtained for the diet enriched with selenium; there was no significant reduction in the level of these elements, and there was even an increase in the concentrations of Fe and K in the bones of rats with implanted LNCaP cells. Particularly, numerous changes in the mineral composition of the bones were generated by enriching the diet with copper. The elements that most often underwent changes (losses) in the bones were cobalt, iron, manganese and molybdenum. The changes observed, most likely induced by the implantation of LNCaP cells, may indicate a disturbance of mineral homeostasis.

Greener Synthesis of Antiproliferative Furoxans via Multicomponent Reactions.

Prostate and bladder cancers are commonly diagnosed malignancies in men. Several nitric oxide donor compounds with strong antitumor activity have been reported. Thus, continuing with our efforts to explore the chemical space around bioactive furoxan moiety, multicomponent reactions were employed for the rapid generation of molecular diversity and complexity. We herein report the use of Ugi and Groebke–Blackburn–Bienaymé multicomponent reactions under efficient, safe, and environmentally friendly conditions to synthesize a small collection of nitric-oxide-releasing molecules. The in vitro antiproliferative activity of the synthesized compounds was measured against two different human cancer cell lines, LNCaP (prostate) and T24 (bladder). Almost all compounds displayed antiproliferative activity against both cancer cell lines, providing lead compounds with nanomolar GI50 values against the cancer bladder cell line with selectivity indices higher than 10.

Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells.

A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin-targeting lead molecules with the acylated 4-aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β-aryl-substituted vinylketones by tert-butyl nitrite in the presence of water as a key step. 4-Methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5-trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3-methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1ab) to the androgen-sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI-26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).

Inhibition of Autophagy Promotes Hemistepsin A-Induced Apoptosis via Reactive Oxygen Species-Mediated AMPK-Dependent Signaling in Human Prostate Cancer Cells.

Chemotherapy is an essential strategy for cancer treatment. On the other hand, consistent exposure to chemotherapeutic drugs induces chemo-resistance in cancer cells through a variety of mechanisms. Therefore, it is important to develop a new drug inhibiting chemo-resistance. Although hemistepsin A (HsA) is known to have anti-tumor effects, the molecular mechanisms of HsA-mediated cell death are unclear. Accordingly, this study examined whether HsA could induce apoptosis in aggressive prostate cancer cells, along with its underlying mechanism. Using HsA on two prostate cancer cell lines, PC-3 and LNCaP cells, the cell analysis and in vivo xenograft model were assayed. In this study, HsA induced apoptosis and autophagy in PC-3 cells. HsA-mediated ROS production attenuated HsA-induced apoptosis and autophagy after treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, autophagy inhibition by 3-MA or CQ is involved in accelerating the apoptosis induced by HsA. Furthermore, we showed the anti-tumor effects of HsA in mice, as assessed by the reduced growth of the xenografted tumors. In conclusion, HsA induced apoptosis and ROS generation, which were blocked by protective autophagy signaling.

Heterodinuclear Cu–Gd (3d-4f) complex with di-compartmental Schiff base ligand in biological activity: Synthesis, crystal structure, catecholase activity and DNA & BSA-binding studies

A dinuclear CuII-GdIII Schiff base complex (a di-compartmental Schiff base ligand derived from o-vanillin) nominated as: 1,3-propanediyl-bis(2-iminomethylene-6-methoxy-phenol) (H2valpn) was synthesized in two steps. To characterize the compounds, single-crystal X-ray crystallography, UV–Vis spectroscopy, IR spectroscopy, and elemental analyses were used. The crystalline sample of the heterodinuclear complex revealed the structure of general formula [(valpn) (H2O) CuII GdIII (NO3)3], with the copper ion located in a square pyramidal section (with an axial aqua ligand) and the gadolinium (III) ion located in the open compartment, in which 10 oxygen atoms from three chelating nitrate ions and a Schiff base ligand surrounded it. To study the applications of the complex, the binding affinity of the complex with FS-DNA was studied by UV–Vis spectroscopy, fluorescence spectroscopy, viscosity measurements, cyclic voltammetry (CV) and circular dichroism (CD). From all of these methods, intercalation was suggested as the main mode of binding. The complex was also checked in interaction with Bovine serum albumin (BSA) by using UV–Vis and fluorescence spectroscopy. Cytotoxicity was tested by MTT assay toward HeLa, LNCaP, and MCF-7 cancer cell lines. Moreover, the docking calculation was performed and these results confirmed the experimental results. The mechanism and kinetics of the catalytic activity of the complex in the oxidation reaction of 3,5-di-tert-butylcatechol, was studied at 298 K.