Human Prostate Cancer Cells Research Articles

Investigation of The Effects of Extraction Polarity Change on the Bioactivity of Eruca Vesicaria

Eruca vesicaria (arugula) plant is frequently used today as a daily food source that contains a rich variety of minerals and vitamins, especially vitamin C. It also contains a high percentage of phenolic compounds which are structures that plants develop to protect themselves from harmful organisms. Phenolic compounds found in plants are obtained by different extraction methods and have a high antioxidant effect. In this study, we report, anticancer activity extract from Eruca vesicaria against human prostate cancer cells (PC-3) in vitro. The phenolic substances contained in the plant were obtained in different concentrations by the extraction technique based on the polarity difference. HPLC and total phenol content were determined to perform extraction content analysis. According to in vitro MTT cell proliferation assay, it acted at high concentrations, regardless of polarity differences. The highest cytotoxic effect was observed in extract extracted with 50% ethanol concentration. It has been observed that it has an anticancer effect compared to the determination of total phenol content. Also, as a result of 24-hour MIC analysis, it shows antibacterial properties according to agent concentration. As a result of this study, it adds many new information to the literature, but also provides guidance for future research.

Development of tripeptide-cyclotriphosphazene derivatives: In vitro cytotoxicity, genotoxicity studies and molecular docking analysis within ovarian and prostate cancer cell line receptors

Peptide-phosphazene compounds are important compounds of growing interest in biomedical research and have potential therapeutic effects. The tripeptide-cyclotriphosphazenes conjugates were synthesized and analyzed for their molecular docking analysis, visualizing their binding profiles within various cancer cell line receptors and tested in vitro cytotoxic and genotoxic properties. Determining in vitro cytotoxic studies of obtained compounds displayed cytotoxic effect against two selected human cancer cell lines, including ovarian (A2780) and prostate (PC-3), cancer cells. The compound DTAP demonstrated significantly higher efficacy at 100 µM in the PC-3 cancer cell line compared to the reference drug docetaxel at 50 µM. Among the tripeptide-phosphazene conjugtates, DTGG demonstrates the most promising anticancer activity with a logIC50 of 1.23 µM, forming five hydrogen bonds and a favorable salt bridge interaction, along with several hydrophobic interactions, thereby stabilizing its binding within the human ovarian tumor domain based on molecular docking analysis. The derivative DTGP emerges as the most potent among the DTG derivatives, achieving a ΔG model value of −108 kcal/mol, primarily due to a π-cationic interaction with the LYS204 amino acid in chain C, which significantly enhances its binding affinity. Additionally, DNA damage studies on human ovarian and prostate cancer cell lines determined that cell death due to DNA damage was the basis of the decrease in cell viability. These results support the evaluation of the compounds as potential drug candidates.

Advancing Anticancer Drug Discovery: Leveraging Metabolomics and Machine Learning for Mode of Action Prediction by Pattern Recognition.

A bottleneck in the development of new anti-cancer drugs is the recognition of their mode of action (MoA). Metabolomics combined with machine learning allowed to predict MoAs of novel anti-proliferative drug candidates, focusing on human prostate cancer cells (PC-3). As proof of concept, 38 drugs are studied with known effects on 16 key processes of cancer metabolism, profiling low molecular weight intermediates of the central carbon and cellular energy metabolism (CCEM) by LC-MS/MS. These metabolic patterns unveiled distinct MoAs, enabling accurate MoA predictions for novel agents by machine learning. The transferability of MoA predictions based on PC-3 cell treatments is validated with two other cancer cell models, i.e., breast cancer and Ewing's sarcoma, and show that correct MoA predictions for alternative cancer cells are possible, but still at some expense of prediction quality. Furthermore, metabolic profiles of treated cells yield insights into intracellular processes, exemplified for drugs inducing different types of mitochondrial dysfunction. Specifically, it is predicted that pentacyclic triterpenes inhibit oxidative phosphorylation and affect phospholipid biosynthesis, as confirmed by respiration parameters, lipidomics, and molecular docking. Using biochemical insights from individual drug treatments, this approach offers new opportunities, including the optimization of combinatorial drug applications.

Circ_0001047 inhibits prostate cancer progression and enhances abiraterone sensitivity via miR-122-5p/FKBP5/PHLPP1/AKT axis in vitro

Prostate cancer (PCa), with high heterogeneity and poor prognosis, is one of the most common malignant tumors in men. Circular RNAs (circRNAs) have been identified in tumor progression and resistance to medication in numerous studies. However, the role of circ_0001047 in PCa is unclear. In this research, we found that circ_0001047 had low expression in PCa cells and tissues and was negatively correlated with testosterone secretion in vivo. Overexpression of circ_0001047 inhibited the proliferation, migration, invasion, and anti-apoptotic abilities of human PCa cells in vitro. Mechanistically, circ_0001047 promoted the expression of FKBP5 through sponge adsorption of miR-122-5p and then inhibited the proliferation, anti-apoptotic migration, and invasion abilities of PCa cells. In addition, overexpression of circ_0001047 enhanced the sensitivity of PCa cells to abiraterone by inhibiting AKT phosphorylation activation through upregulation of FKBP5/PHLPP1. This study revealed a novel mechanism by which circ_0001047 regulates PCa progression and treatment sensitivity via the miR-122-5p/FKBP5/PHLPP1/AKT axis. These findings deepen our comprehension of the molecular mechanisms in latent PCa progression and treatment resistance.Graphical

Novel Zn(II), Co(II) and Cu(II) diflunisalato complexes with neocuproine and their exceptional antiproliferative activity against cancer cell lines.

Three novel complexes of deprotonated diflunisal (dif) with neocuproine (neo) were synthesized and characterized via elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl(dif)(neo)], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of neo in a bidentate chelate mode, and one chlorido ligand and dif is bonded in either a monodentate mode via one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode via both carboxylate oxygen atoms in 3. All three compounds demonstrated remarkable antiproliferative activity against human prostate (PC-3), colon (HCT116) and breast (MDA-MB-468) cancer cell lines with IC50 values in the nanomolar range, with the lowest values observed in the case of PC-3 and MDA-MB-468 with 2 (20.0 nM) and 3 (31.1 nM), respectively. Moreover, complex 2, as the most active, was further investigated for its potential to induce perturbations in the cell cycle of PC-3 cells. The results indicated an induction of caspase-independent apoptosis. The interaction of the complexes with genomic DNA isolated from the respective cancer cell lines was evaluated for the intercalative mode, with binding strength correlated with the antiproliferative activity against PC-3 and MDA-MB-468 cancer cell lines.

Cancer cell-selective induction of mitochondrial stress and immunogenic cell death by PT-112 in human prostate cell lines

PT-112 is a novel immunogenic cell death (ICD)-inducing small molecule currently under Phase 2 clinical development, including in metastatic castration-resistant prostate cancer (mCRPC), an immunologically cold and heterogeneous disease state in need of novel therapeutic approaches. PT-112 has been shown to cause ribosome biogenesis inhibition and organelle stress followed by ICD in cancer cells, culminating in anticancer immunity. In addition, clinical evidence of PT-112-driven immune effects has been observed in patient immunoprofiling. Given the unmet need for immune-based therapies in prostate cancer, along with a Phase I study (NCT#02266745) showing PT-112 activity in mCRPC patients, we investigated PT-112 effects in a panel of human prostate cancer cell lines. PT-112 demonstrated cancer cell selectivity, inhibiting cell growth and leading to cell death in prostate cancer cells without affecting the non-tumorigenic epithelial prostate cell line RWPE-1 at the concentrations tested. PT-112 also caused caspase-3 activation, as well as stress features in mitochondria including ROS generation, compromised membrane integrity, altered respiration, and morphological changes. Moreover, PT-112 induced damage-associated molecular pattern (DAMP) release, the first demonstration of ICD in human cancer cell lines, in addition to autophagy initiation across the panel. Taken together, PT-112 caused selective stress, growth inhibition and death in human prostate cancer cell lines. Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study.

ONCOLYTIC ACTIVITY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS.

Oncolytic viruses (OVs) are emerging as novel tools in cancer therapy. Oncolytic virotherapy offers an attractive therapeutic combination of tumor-specific killing and immune co-stimulation, therefore amplifying the host immune response against tumors. Moreover, OVs can be engineered for the expression of different immunostimulatory molecules to optimize and enhance the efficacy of oncolytic virotherapy. The effectiveness of OVs has been demonstrated in many preclinical studies for different types of cancers to achieve the aim of personalized cancer therapy. Human respiratory syncytial virus (RSV), an RNA virus of the Pneumoviridae family causes severe lower respiratory tract infections in infants and immunocompromised individuals. Interestingly, the oncolytic activity of RSV demonstrated in human prostate, hepatocellular, and dermal cancer cells is mostly mediated via apoptotic cell death associated with the impaired NF-κB activation or with the defect of the IFNα/β-induced STAT-1 activation. At the same time, the studies on cervical cancer revealed that RSV infection resulted in autophagy activation and apoptosis through the ROS-BAX and TNF- α-mediated pathways. The rational combinations of OVs, including RSV, with other approaches may benefit patients whose response to conventional therapies is limited. Here, we discuss the oncolytic activity of RSV and its potential use against different types of cancer.

1,4-Naphthoquinone thiazoles: Synthesis, crystal structure, anti-proliferative activity, and inverse molecular docking study

In this study, 1,4-naphthoquinone thiazole hybrids were synthesized by reacting 1,4-naphthoquinone thioureas with various α-bromoketones in 78–86 % yields and characterized using 1H NMR, 13C NMR, FT-IR, and HRMS techniques. Furthermore, single crystal x-ray diffraction studies were also performed for 3b and 3c hybrids to determine stereochemistry. Density Functional Theory (DFT) calculations were performed to obtain additional information and to support the x-ray studies. The in vitro anti-proliferative activities of 1,4-naphthoquinone thiazoles were investigated against PC3 human prostate cancer cells. The products 3a–h showed anti-proliferative activity against PC3 cells, and the cell viability studies showed that the IC50 values of compounds 3f and 3e were 20.10 µM and 21.14 µM, respectively, while the other compounds exhibited lesser cytotoxic effects than the former two. Potential target underlying the mechanism of action of the synthesized compounds against prostate cancer was identified using inverse (reverse) docking method. Molecular dynamics simulation was also conducted to confirm the stability of the 3f/enzyme system. It was determined that the solubility in ethanol was better for compounds bearing methyl substituent on X1 location than compounds containing tert‑butyl on the same location. Compounds with F atom on X2 position were more soluble than the others in the corresponding groups.

Synergistic Phytochemical and Pharmacological Actions of Hair RiseTM Microemulsion: A Novel Herbal Formulation for Androgenetic Alopecia and Hair Growth Stimulation.

Androgenetic alopecia (AGA) is a genetic condition characterized by an excessive response to androgens, leading to hairline regression in men and hair thinning at the vertex in women, which can negatively impact self-esteem. Conventional synthetic treatments for AGA are often limited by their side effects. In contrast, Thai medicinal plants offer a promising alternative with fewer adverse effects. This study investigates the synergistic phytochemical and pharmacological effects of a novel Hair RiseTM microemulsion, formulated with bioactive extracts from rice bran (Oryza sativa), shallot bulb (Allium ascalonicum), licorice root (Glycyrrhiza glabra), and corn kernels (Zea mays), for the treatment of hair loss. The microemulsion, in concentrations of 50%, 75%, and 100% (v/v), significantly enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) compared to minoxidil. Additionally, it upregulated critical hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), surpassing standard controls such as minoxidil and purmorphamine. The microemulsion also demonstrated potent anti-inflammatory and antioxidant properties by reducing nitric oxide production and oxidative stress, factors that contribute to inflammation and follicular damage in AGA. Furthermore, Hair RiseTM inhibited 5α-reductase (types 1-3), a key enzyme involved in androgen metabolism, in both human prostate cancer cells (DU-145) and HFDPCs. These findings suggest that Hair RiseTM microemulsion presents a promising natural therapy for promoting hair growth and reducing hair loss via multiple synergistic mechanisms, offering a potent, plant-based alternative to synthetic treatments.

12234 Gα13 Promotes Clonogenic Growth By Increasing Tolerance To Oxidative Metabolic Stress In Prostate Cancer Cells

Abstract Disclosure: D. Wu: None. W. Lim: None. X. Chai: None. V.P. Seshachalam: None. S.A. Rasheed: None. S. Ghosh: None. P.J. Casey: None. Gα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors. Analyses of tumor specimens indicate that Gα13 expression correlates with patient survival in several solid cancers. We previously reported a role for Gα13 in cell migration and invasion in prostate cancer cell lines. Interestingly, patient data supports the notion that mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason scores. Gα13 lower-expressing LNCaP cells also have lower SOD2 protein levels compared to the Gα13 higher-expressing PC3 cells. Hence, we explored the role of Gα13 in prostate tumorigenesis, and its effect on cellular processes such as cell survival and mitochondrial metabolism, in human prostate cancer cell lines PC3 and LNCaP. We stably knocked-down GNA13 expression in PC3 cells and overexpressed GNA13 in LNCaP cells. We found that Gα13 promoted anchorage-independent cell growth in PC3 and LNCaP cell lines, as assessed by soft agar colony formation, spheroid formation, and xenograft tumor growth. Whole-genome transcriptome analyses suggested that Gα13-regulated genes are functionally enriched in the mitochondria compartment and that GNA13 expression positively correlated to SOD2 transcript levels in PC3 cells. We found that silencing GNA13 sensitized PC3 cells to long-term oxidative metabolic stress when cultured in media containing non-glycolytic metabolites, namely galactose, glutamate plus malate, and succinate. Furthermore, Gα13 levels impacted the abundance of SOD2 protein in the mitochondria, as well as SOD2 promoter activity and mRNA expression. In addition, silencing GNA13 increased mitochondrial superoxide levels in PC3 cells when cultured in galactose medium, as assessed by MitoSOX staining and flow cytometry. Moreover, overexpression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent cell growth in PC3 cells. Importantly, anchorage-independent cell growth was not rescued when a catalytically-inactive SOD2(Q167A) mutant was expressed. Likewise, stable knockdown of SOD2 suppressed the effect of overexpression of Gα13 on anchorage-independent cell growth in LNCaP cells. We propose a novel biological route of Gα13-mediated anchorage-independent growth and response to oxidative metabolic stress through regulation of SOD2 expression in prostate cancer cells. Given that SOD2 protein levels correlate with prostate cancer Gleason grade, identifying the upregulated GPCRs that signal through Gα13 in prostate cancer could lead to novel preventive or therapeutic strategies. Presentation: 6/1/2024

Relative biological effectiveness of clinically relevant photon energies for the survival of human colorectal, cervical, and prostate cancer cell lines

Objective.Relative biological effectiveness (RBE) differs between radiation qualities. However, an RBE of 1.0 has been established for photons regardless of the wide range of photon energies used clinically, the lack of reproducibility in radiobiological studies, and outdated reference energies used in the experimental literature. Moreover, due to intrinsic radiosensitivity, different cancer types have different responses to radiation. This study aimed to characterize the RBE of clinically relevant high and low photon energiesin vitrofor three human cancer cell lines: HCT116 (colon), HeLa (cervix), and PC3 (prostate).Approach.Experiments were conducted following dosimetry protocols provided by the American Association of Physicists in Medicine. Cells were irradiated with 6 MV x-rays, an192Ir brachytherapy source, 225 kVp and 50 kVp x-rays. Cell survival post-irradiation was assessed using the clonogenic assay. Survival fractions were fitted using the linear quadratic model, and survival curves were generated for RBE calculations.Main results.Cell killing was more efficient with decreasing photon energy. Using 225 kVp x-rays as the reference, the HCT116 RBESF0.1for 6 MV x-rays,192Ir, and 50 kVp x-rays were 0.89 ± 0.03, 0.95 ± 0.03, and 1.24 ± 0.04; the HeLa RBESF0.1were 0.95 ± 0.04, 0.97 ± 0.05, and 1.09 ± 0.03, and the PC3 RBESF0.1were 0.84 ± 0.01, 0.84 ± 0.01, and 1.13 ± 0.02, respectively. HeLa and PC3 cells had varying radiosensitivity when irradiated with 225 and 50 kVp x-rays.Significance.This difference supports the notion that RBE may not be 1.0 for all photons through experimental investigations that employed precise dosimetry. It highlights that different cancer types may not have identical responses to the same irradiation quality. Additionally, the RBE of clinically relevant photons was updated to the reference energy of 225 kVp x-rays.

Determination of the interactions of a schiff base with different targets via molecular docking and cytotoxic activity studies

The pyrimidine nucleus is a vital pharmacophore that exhibits excellent pharmacological activity. A Schiff base containing a pyrimidine nucleus was obtained in two steps. This compound was assessed on the human prostate (PC3) and liver (HepG2) cancer cell lines using the MTT method. The prepared compound 3 was determined to have a high cytotoxic effect towards prostate cancer with an IC50 value of 9.32 μM. Since experimental prostate and liver cancer studies were examined, the molecular docking study's target structures were determined accordingly. In molecular docking studies, compound 3 interacted in silico with the crystal structure of the human HER2 kinase domain (PDB Id: 3PP0), the crystal structure of VEGFR-2 (PDB Id: 4ASD), and the crystal structure of EGFR tyrosine kinase (PDB Id: 4HJO), respectively. As a result of these interactions, binding energy values were calculated, and binding modes were determined. Additional in vitro and in vivo experiments targeting other cancer cell lines will provide deeper insight into the anticancer spectrum of this compound and new studies on this compound will be planned in the following years. Furthermore, optimizing and studying such pyrimidine-based Schiff base compounds for improved selectivity and potency against prostate cancer is also considered to be valuable as it may increase the potential to capture potential drug candidates.

Investigation of Biological Activity of Squamarina cartilaginea (With.) P. James Species Distributed in Türkiye

In this study, the methanol extract of Squamarina cartilaginea, a species distributed in Türkiye, was investigated for its antimicrobial, antioxidant, cytotoxic, and DNA protective effects. The chemical composition of the extract was elucidated through spectroscopic determination of total phenols, total flavonoids, and chromatographic quantification of usnic acid. Antimicrobial activity was assessed using the disk diffusion method, revealing a significant zone of inhibition with a diameter of 17.5 mm against M. luteus and S. aureus. The antioxidant activity was evaluated through scavenging activities against DPPH and ABTS radicals, demonstrating a concentration-dependent potent scavenging activity against ABTS radicals. Cytotoxic activity was determined using the MTT method on DU-145 (Human Prostate Cancer Cell Line) and Colo 205 (Human Colon Cancer Cell Line) cell lines. The extract exhibited strong cytotoxic activity against the Colo 205 cell line, with a viability percentage of 33.16±2.01 at a concentration of 3.906 µg/mL. Furthermore, the S. cartilaginea extract demonstrated DNA protective activity on pBR322 plasmid DNA against UV and H2O2 exposure.

Discovery of a Highly Potent PROTAC Degrader of p300/CBP Proteins for the Treatment of Enzalutamide-Resistant Prostate Cancer.

Prostate cancer therapies against androgen receptor (AR) eventually develop lethal resistance; thus, exploring new therapeutic approaches is urgent for prostate cancer treatment. Acetyltransferase p300/CBP are key coactivators for AR-mediated transcription and represent promising therapeutic targets to inhibit AR activity in prostate cancer. We describe the design synthesis and evaluation of a new class of p300/CBP PROTAC degraders. We identified an excellent p300/CBP degrader MJP6412, which effectively induced degradation of p300/CBP proteins, downregulated AR target genes, and inhibited cell growth of human prostate cancer cell lines and enzalutamide-resistant cells with IC50 even at nanomolar concentrations. Furthermore, MJP6412 demonstrated significant inhibition of tumor growth in a VCaP xenograft model. Collectively, MJP6412 is a promising lead compound for the treatment of prostate cancer, especially enzalutamide-resistant prostate cancer.

Investigating the antioxidant and anticancer potential of Daucus spp. extracts against human prostate cancer cell line C4-2, and lung cancer cell line A549

The study evaluated 297 carrot germplasm lines, focusing on 52 cultivars to explore their therapeutic potential and address challenges related to the accessibility and affordability of nutraceuticals and health promoting foods. The investigation explores the application of DNA barcoding using the ITS region for precise species identification, highlighting genetic diversity among the examined cultivars. Through ITS sequence-based analysis and phylogenetic examination, six diverse Daucus spp. genotypes were differentiated and classified into distinct groups, indicating the presence of vast genetic variation. Evaluation of antioxidant activities using the DPPH radical scavenging assay revealed varying degrees of scavenging ability among genotypes with SKAU-C-15, SKAU-C-17, and SKAU-C-16 exhibiting the highest activity, suggesting their potential for antioxidant-rich products. Thin Layer Chromatography (TLC) bioautography confirmed the presence of bioactive compounds in carrot extracts responsible for their antioxidant properties. In cell culture studies, specific carrot genotype extracts demonstrated potential anti-proliferative and anti-invasive effects on recurrent prostate cancer cell line - C4-2 (SKAU-C-30, SKAU-C-10, and SKAU-C-42) and non-small cell lung cancer cell line - A549 (SKAU-C-18 and SKAU-C-11) cancer cells, as indicated by MTT assay, wound healing assay, and Colony Forming Unit assay. These findings suggest the promising therapeutic potential of carrot genotypes for developing anti-cancer functional foods, nutraceuticals and health supplements.Therefore, the study contributes to the nutrition security, paving the way for advancements in functional foods and health applications, particularly in cancer treatment and prevention.

Cellular Uptake and Computational Analysis of [131I]-Xanthine and [131I]-Hypoxanthine in Human Prostate Cancer Cell Line (LNCaP)

Cellular Uptake and Computational Analysis of [131I]-Xanthine and [131I]-Hypoxanthine in Human Prostate Cancer Cell Line (LNCaP)

Morin promotes autophagy in human PC3 prostate cancer cells by modulating AMPK/mTOR/ULK1 signaling pathway

AMP-activated protein kinase (AMPK) suppresses tumorigenesis by modulating autophagy and apoptosis. This study evaluated the impact of Morin on PC3 prostate cancerous cells by examining the AMPK/ mechanistic target of rapamycin (mTOR)/ ULK1 (UNC-51-like kinase 1) pathway and autophagy process. The PC3 cells were treated with Morin (50 µg/ml) and AICAR (an AMPK activator). Cell viability, apoptosis, autophagy, and level of phosphorylated and non-phosphorylated ULK1, AMPK, and mTOR, as well as LC3B/LC3A, have been investigated. Through DAPI staining, measurement of Bax/Bcl-2 ratio, Caspase activity, and Annexin V/PI method, it has been revealed that Morin induces apoptosis and reduces the growth of PC3 cells. Morin enhanced the protein level of phosphorylated AMPK (p-AMPK) and ULK1 (p-ULK1) and decreased the expression of phosphorylated mTOR (p-mTOR) in the PC3 cells. Morin could also increase the LC3B/LC3A ratio, Acridine Orange-positive cells, expression of Beclin-1 and ATG5 genes, and decrease the p62 protein level indicating autophagy-inducing. AICAR (an AMPK activator) enhanced the impact of Morin on apoptosis, cell growth, and expression of LC3B, p-AMPK, p-ULK1, and p-mTOR proteins in the PC3 cells. These findings suggest that Morin induces apoptotic and autophagic cell death by activating AMPK and ULK1 and suppressing mTOR pathways.

Bone sialoprotein stimulates cancer cell adhesion through the RGD motif and the αvβ3 and αvβ5 integrin receptors.

Being implicated in bone metastasis development, bone sialoprotein (BSP) expression is upregulated in patients with cancer. While BSP regulates cancer cell adhesion to the extracellular matrix, to the best of our knowledge, the specific adhesive molecular interactions in metastatic bone disease remain unclear. The present study aimed to improve the understanding of the arginine-glycine-aspartic acid (RGD) sequence of BSP and the integrin receptors αvβ3 and αvβ5 in BSP-mediated cancer cell adhesion. Human breast cancer (MDA-MB-231), prostate cancer (PC-3) and non-small cell lung cancer (NSCLC; NCI-H460) cell lines were cultured on BSP-coated plates. Adhesion assays with varying BSP concentrations were performed to evaluate the effect of exogenous glycine-arginine-glycine-aspartic acid-serine-proline (GRGDSP) peptide and anti-integrin antibodies on the attachment of cancer cells to BSP. Cell attachment was assessed using the alamarBlue® assay. The present results indicated that BSP supported the adhesion of cancer cells. The RGD counterpart GRGDSP peptide reduced the attachment of all tested cancer cell lines to BSP by ≤98.4%. Experiments with anti-integrin antibodies demonstrated differences among integrin receptors and cancer cell types. The αvβ5 antibody decreased NSCLC cell adhesion to BSP by 84.3%, while the αvβ3 antibody decreased adhesion by 14%. The αvβ3 antibody decreased PC-3 cell adhesion to BSP by 46.4%, while the αvβ5 antibody decreased adhesion by 9.5%. Adhesion of MDA-MB-231 cells to BSP was inhibited by 54.7% with αvβ5 antibody. The present results demonstrated that BSP-induced cancer cell adhesion occurs through the binding of the RGD sequence of BSP to the cell integrin receptors αvβ3 and αvβ5. Differences between cancer types were found regarding the mediation via αvβ3 or αvβ5 receptors. The present findings may explain why certain cancer cells preferentially spread to the bone tissue, suggesting that targeting the RGD-integrin binding interaction could be a promising novel cancer treatment option.

New cyano-acrylamide derivatives incorporating the thiophene moiety: Synthesis, anti-cancer, gene expression, DNA fragmentation, DNA damage, and in silico studies

New cyano-acrylamide derivatives bearing the thiophene structure were prepared and rigorously characterized. Thus, the reaction of diethyl 5-(2-cyanoacetamido)-3-methylthiophene-2,4-dicarboxylate with aldehydes in the presence of piperidine afforded the title compounds in very good to excellent yields (range 81-96%, mean 91%). All the newly synthesized compounds were evaluated as anti-cancer agents against five human cancer cell lines namely, MCF7 (human Caucasian breast adenocarcinoma), PC3 (human prostate cancer cell line), HepG2 (Human hepatocellular carcinoma), PACA2 (epithelial cell line derived from tumor tissue of pancreas), and BJ1 (normal skin fibroblast). While most of the compounds showed good activity against MCF-7, they showed limited activity against PC3, HepG2, and PACA2. Compound 9 showed potent anti-cancer activity against the PACA2 cell line with IC50 131.18 µM compared with the reference drug (doxorubicin, IC50 52.06 µM), while compound 10 exhibited potent anti-cancer activity against HePG2 cell lines with IC50 24.51 µM compared to the positive control (doxorubicin, IC50 39.73 µM). The gene expression, DNA fragmentation, and DNA damage of the most promising compounds were discussed. Additionally, compounds 9 and 10 showed favorable binding energies and strong interactions with CDK2, EGFR, ERα, VEGFFR, and Topoisomerase II receptors in the molecular docking simulation. These results suggest that these compounds have the potential to be effective candidates for anti-cancer therapy. Additionally, the in-silico ADMET profiles indicated that these compounds adhere to the Lipinski rules, indicating favorable physicochemical properties. These findings further support their potential for continued drug development efforts.

Engineering of Layer-by-layer Acetate-coated Paclitaxel Loaded Poly(lactide-co-glycolide) Acid Nanoparticles for Prostate Cancer Therapy- in vitro

It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy.