Prostate Cancer Cell Lines DU145 Research Articles

Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis

Despite growing evidence implicating the calcium-activated chloride channel anoctamin1 (ANO1) in cancer metastasis, its direct impact on the metastatic potential of prostate cancer and the possible significance of epigenetic alteration in this process are not fully understood. Here, we show that ANO1 is minimally expressed in LNCap and DU145 prostate cancer cell lines with low metastatic potential but overexpressed in high metastatic PC3 prostate cancer cell line. The treatment of LNCap and DU145 cells with DNMT inhibitor 5-aza-2′-deoxycytidine (5-Aza-CdR) potentiates ANO1 expression, suggesting that DNA methylation is one of the mechanisms controlling ANO1 expression. Consistent with this notion, hypermethylation was detected at the CpG island of ANO1 promoter region in LNCap and DU145 cells, and 5-Aza-CdR treatment resulted in a drastic demethylation at promoter CpG methylation sites. Upon 5-Aza-CdR treatment, metastatic indexes, such as cell motility, invasion, and metastasis-related gene expression, were significantly altered in LNCap and DU145 cells. These 5-Aza-CdR-induced metastatic hallmarks were, however, almost completely ablated by stable knockdown of ANO1. These in vitro discoveries were further supported by our in vivo observation that ANO1 expression in xenograft mouse models enhances the metastatic dissemination of prostate cancer cells into tibial bone and the development of osteolytic lesions. Collectively, our results help elucidate the critical role of ANO1 expression in prostate cancer bone metastases, which is epigenetically modulated by promoter CpG methylation.

Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells

KDM2B, a histone lysine demethylase, is expressed in a plethora of cancers. Earlier studies from our group, have showcased that overexpression of KDM2B in the human prostate cancer cell line DU-145 is associated with cell adhesion, actin reorganization, and improved cancer cell migration. In addition, we have previously examined changes of cytosolic Ca2+, regulated by the pore-forming proteins ORAI and the Ca2+ sensing stromal interaction molecules (STIM), via store-operated Ca2+ entry (SOCE) in wild-type DU-145. This study sought to evaluate the impact of KDM2B overexpression on the expression of key molecules (SGK1, Nhe1, Orai1, Stim1) and SOCE. Furthermore, this is the first study to evaluate KDM2B expression in circulating tumor cells (CTCs) from patients with prostate cancer. mRNA levels for SGK1, Nhe1, Orai1, and Stim1 were quantified by RT-PCR. Calcium signals were measured in KDM2B-overexpressing DU-145 cells, loaded with Fura-2. Blood samples from 22 prostate cancer cases were scrutinized for KDM2B expression using immunofluorescence staining and the VyCAP system. KDM2B overexpression in DU-145 cells increased Orai1, Stim1, and Nhe1 mRNA levels and significantly decreased Ca2+ release. KDM2B expression was examined in 22 prostate cancer patients. CTCs were identified in 45 % of these patients. 80 % of the cytokeratin (CK)-positive patients and 63 % of the total examined CTCs exhibited the (CK + KDM2B + CD45−) phenotype. To conclude, this study is the first to report increased expression of KDM2B in CTCs from patients with prostate cancer, bridging in vitro and preclinical assessments on the potentially crucial role of KDM2B on migration, invasiveness, and ultimately metastasis in prostate cancer.

Biogenic silver nanoparticle synthesis using orange peel extract and its multifaceted biomedical application.

The aim of this study was to employ an agro-industrial byproduct, specifically Citrus sinensis peels, as a reservoir of polyphenols. The natural chemicals present in C. sinensis peels serve as reducing agents in an environmentally benign method for synthesizing silver nanoparticles (AgNPs). This methodology not only provides a more environmentally friendly method for synthesizing nanoparticles but also enhances the value of agricultural waste, emphasizing the sustainable utilization of resources. In our study, AgNPs were successfully synthesized using peel aqueous exact of C. sinensis and then their various biological activity has been investigated. The synthesized AgNPs were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and transmission electron microscopy (TEM) analysis. Furthermore, their effectiveness in inhibiting growth and biofilm formation of Escherichia coli, Staphylococcus aureus, and Candida albicans has been investigated. The minimum inhibitory concentrations (MIC) for E. coli and S. aureus were both 32μg/mL, and for C. albicans, it was 128µg/mL. At 250µg/mL of AgNPs, 94% and 92% biofilm inhibition were observed against E. coli and S. aureus, respectively. Furthermore, AgNPs demonstrated significant toxic effects against human prostate cancer cell line DU145 as investigated by anti-apoptotic, 4',6-diamidino-2-phenylindole (DAPI), reactive oxygen species (ROS), and acridine orange/ethidium bromide (AO/EtBr) assays. We also conducted uptake analysis on these pathogens and cancer cell lines to preliminarily investigate the mechanisms underlying their toxic effects. These findings confirm that AgNPs can serve as a cost-effective, non-toxic, and environmentally friendly resource for green synthesis of medicinal AgNPs. Moreover, this approach offers an alternative recycling strategy that contributes to the sustainable use of biological by-products.

Effects of crotamine in human prostate cancer cell line

Our study presents the anticancer potential of crotamine from Crotalus durissus terrificus in human prostate cancer cell line DU-145. Crotamine isolation was conducted through RP-FPLC, its molecular mass analyzed by MALDI-TOF was 4881.4 kDa, and N-terminal sequencing confirmed crotamine identity. Crotamine demonstrated no toxicity and did not inhibit migration in HUVEC cells. Although no cell death occurred in DU-145 cells, crotamine inhibited their migration. Thus, crotamine presented potential to be a prototype of anticancer drug.

Synthesis and SAR investigation of biphenylaminoquinoline derivatives with benzyloxy substituents as promising anticancer agents.

The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the meta or para position of the biphenyl ring categorized into two distinct groups: [4,3']biphenylaminoquinoline-substituted and [3,3']biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure-activity relationship. Furthermore, we determined the IC50 values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3']biphenylaminoquinoline derivative 7j displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC50 values of 1.05 μM, 0.98 μM, 0.38 μM, and 0.17 μM, respectively. This highly promising outcome underscores the potential of [3,3']biphenylaminoquinoline 7j for further investigation as a prospective anticancer agent in future research endeavors.

Total phenolic content, phytochemical profile and cytotoxic effects of endemic Alyssum floribundum (Brassicaceae) from Turkey

Alyssum genus has many ethnobotanical uses due to the bioactive compounds it contains (glucosinolates, hydrocarbons, fatty acids and phenolic compounds, etc.). The objective of this study was to assess the total phenolic content, potential bioactive components and cytotoxic effects of ethanol extracts obtained from different parts (root, stem and leaf) of Alyssum floribundum. The Folin-Ciocalteu colorimetric method was utilized to measure the total phenolic content of all extracts. The total phenolic content of different parts A. floribundum were 12.6 ± 02, 8.2 ± 1.2 and 4.9 ± 0.8 mg GAE/g, respectively. The bioactive compounds of different parts A. floribundum were shown by employing gas chromatography coupled to mass spectrometry (GC/MS) and were identified to contain 30 different chemical components in all parts of the plant. The cytotoxic effect was evaluated using the xCELLigence method on the DU-145 prostate cancer cell line. The root, stem and leaf extracts of A. floribundum displayed the strongest cytotoxicity against the DU-145 prostate cancer cell act in a dose-dependent manner after 24 and 48 h with IC50 values of various concentrations after 24 and 48 h were calculated and determined as 192.1–157.4 µg/mL, 29.12–26.93 µg/mL and 226.4–80.23 µg/mL, respectively.

Isolation, Identification and Chemical Modification of Bufadienolides from Bufo melanostictus Schneider and Their Cytotoxic Activities against Prostate Cancer Cells.

The traditional Chinese medicine toad venom (Venenum bufonis) has been extensively used to treat various diseases, including cancers, in China and other Southeast Asian countries. The major constituents of toad venom, e.g., bufadienolides and alkaloids, exhibit broad-spectrum pharmacological effects in cancers. Herein, two new bufadienolides (1 and 2), along with eleven known compounds (3-13) were successfully isolated from Bufo melanostictus Schneider. Their structures were elucidated by extensive spectroscopic data and X-ray diffraction analysis. Furthermore, four lactam derivatives were synthesized through the transformation of bufadienolides lactones. The inhibitory effects of these compounds against human prostate cancer cell lines PC-3 and DU145 were evaluated. The outcomes indicated a notable trend, with a substantial subset displaying nanomolar range IC50 values against PC-3 and DU145 cells, underscoring their pronounced cytotoxicity. Moreover, a noteworthy distinction surfaces, wherein lactones consistently outperformed their lactam counterparts, further validating their heightened potency for the treatment of prostate cancer. This study contributes significant preclinical evidence substantiating the therapeutic viability of bufadienolides and toad venom as intervention strategies for prostate cancer.

Abstract 3036: Sensitivity of ONC201/TIC10 cancer therapeutic on neuroendocrine prostate cancer (NEPC) and neuroendocrine differentiation (NED)

Abstract Although androgen deprivation therapy and androgen receptor (AR) blockade are highly effective therapies for metastatic prostate cancer (PCa), most patients develop resistance, leading to castration-resistant prostate cancer (CRPC). A subset of CRPC shows neuroendocrine prostate cancer (NEPC) features, which are associated with poor prognosis and limited therapeutic strategies. NEPC is characterized by oncogenic driver activation and epigenetic changes, partly controlled by transcription factors like BRN2 and SOX2. AR has been shown to suppress BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2 (Bishop et al., 2017). Dordaviprone (ONC201/TIC10) is a first-in-class small molecule that antagonizes DRD2, induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and activates the integrated stress response (ISR). Neuroendocrine tumors express significant DRD2 levels, suggesting ONC201 as a potential therapeutic strategy in NEPC or when drivers for disease progression are overexpressed (OE). PCa cell lines PC3, DU145, LNCaP, and 22RV1 are ONC201 sensitive, with IC50=2.87 μM, 3.18 μM, 1.31 μM, and 1.16 μM, respectively (Ding et al., 2023). To characterize the association of BRN2/SOX2 dysregulation with ONC201 sensitivity, we transiently OE BRN2/SOX2 in PCa. We hypothesized that markers of neuroendocrine differentiation (NED), activation of the ISR, TRAIL, and ClpP and dopamine receptor expression contribute to NEPC cell death and sensitivity to ONC201. We performed CellTiter-Glo experiments to assess viability after 96 hours ± BRN2 OE. DU145 cells with BRN2 OE increased their sensitivity to ONC201 (IC50=2.75 µM) compared to empty vector (IC50=3.03 µM). Colony formation assays were conducted in PCa and analyzed 7 days after ONC201 treatment to show ONC201 effect on PCa cell lines. DU145 was treated at 0.5, 1, and 2 µM of ONC201. There were 95 ± 3.22 colonies for the control group, 83 ± 5.22 colonies with 0.5 µM, 74 ± 3.64 colonies with 1 µM, and 8 ± 2.03 colonies with 2 µM ONC201. DU145 showed a significant reduction in colony-forming ability when treated with 1 and 2 uM ONC201 compared to the control, with P values of <0.05 and <0.0001, respectively. We OE BRN2 and observed changes in NED markers and ISR pathway. In PC3, FoxO1 and ATF4 levels increased. In DU145, FoxO1, ENO2, PGP9.5, CgA, and ATF4 levels decreased. We reveal that DU145 OE at 48 hours does not result in greater expression of NEPC markers. BRN2 OE significantly increased PCa cell sensitivity to ONC201 and was evident without an increase in common phenotypical markers used for NEPC assessment (FoxO1, ENO2, PGP9.5, CgA). Expression change was not shown when PCa had an integral AR pathway. Ongoing efforts are observing ONC201 treatment effects on NED markers and the TRAIL pathway due to BRN2 OE and showing increased sensitivity of PCa to ONC201 with BRN2 OE. Citation Format: Elizabeth C. Ding, Maximilian Pinho-Schwermann, Shengliang Zhang, Connor Purcell, Wafik S. El-Deiry. Sensitivity of ONC201/TIC10 cancer therapeutic on neuroendocrine prostate cancer (NEPC) and neuroendocrine differentiation (NED) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3036.

A Bee Trp-Arg Dense Peptide with Antiproliferation Efficacy against the Prostate Cancer Cell Line DU145.

Prostate cancer accounts for 14% of male cancer-related fatalities in the UK. Given the challenges associated with hormone-based therapies in the context of androgen-independent prostate cancer, there is an imperative need for research into anticancer drugs. N0821, a peptide belonging to the Trp-Arg dense region and derived from the homologous region of various bee species, shows substantial potential for an anticancer effect. Both MTT assays and 3D spheroid assays were conducted to substantiate its antiproliferation potential and strongly indicated the antiproliferation effect of N0820 (WWWWRWWRKI) and N0821 (YWWWWRWWRKI). Notably, the mechanism underlying this effect is related to the downregulation of CCNA2 and the upregulation of CCNE1. Cell cycle arrest results from the reduction of CCNA2 in the S/G2 phase, leading to the accumulation of CCNE1. Our peptides were predicted to make an α-helix structure. This can act as an ion channel in the cell membrane. Therefore, we analyzed genes implicated in the influx of calcium ions into the mitochondria. Trp-Arg dense-region peptides are known for their antibacterial properties in targeting cell membranes, making the development of resistance less likely. Hence, further research in this area is essential and promising.

Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.

Proteasome inhibitors such as Bortezomib represent an established type of targeted treatment for several types of hematological malignancies, including multiple myeloma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma, based on the cancer cell's susceptibility to impairment of the proteasome-ubiquitin system. However, a major problem limiting their efficacy is the emergence of resistance. Their application to solid tumors is currently being studied, while simultaneously, a wide spectrum of hematological cancers, such as Myelodysplastic Syndromes show minimal or no response to Bortezomib treatment. In this study, we utilize the prostate cancer cell line DU-145 to establish a model of Bortezomib resistance, studying the underlying mechanisms. Evaluating the resulting resistant cell line, we observed restoration of proteasome chymotrypsin-like activity, regardless of drug presence, an induction of pro-survival pathways, and the substitution of the Ubiquitin-Proteasome System role in proteostasis by induction of autophagy. Finally, an estimation of the oxidative condition of the cells indicated that the resistant clones reduce the generation of reactive oxygen species induced by Bortezomib to levels even lower than those induced in non-resistant cells. Our findings highlight the role of autophagy and oxidative stress regulation in Bortezomib resistance and elucidate key proteins of signaling pathways as potential pharmaceutical targets, which could increase the efficiency of proteasome-targeting therapies, thus expanding the group of molecular targets for neoplastic disorders.

Exploring substituted 3,4-dihydropyrimidinone and thione derivatives as anti-prostate cancer agents: Computational screening, synthesis, characterization, and in vitro efficacy assessment

Despite decades of research, anticancer medication therapy is still largely constrained to prevent growth and limit the spread of tumour cells. To speed up the process of finding anticancer drugs, exploring novel therapeutic macromolecules and identifying the right small molecules using an integration of computational and experimental approaches is a recent tactic adopted by investigators. In the present study, we designed and created a library of 200 ligands with 3,4-dihydropyrimidinones or their thiones linked with imidazolidinones through amide linkage and explored the extent of their in vitro anticancer activity towards human topoisomerase IIalpha (TOP2α or TOP2A) using DU-145 and PC-3 prostate cancer cell lines using the SRB assay method. This was accomplished by the molecular docking and synthesis of the titled compounds using a series of organic nucleophilic addition reactions, including the Biginelli one-pot condensation reaction. The preliminary physical character evaluation was employed for the synthesized compounds, and the structural parameters were analyzed using FTIR, proton NMR, 13C NMR, and LC-MS/MS. The anti-prostate cancer activity of the prepared Biginelli analogues was evaluated against cancer cell lines and mild-to-moderate reduction in the viability of cell lines was observed with compounds 5, 6, 9, 14, 15, 16, 17, and 19. Among them, compounds 5, 14, 15, and 16 exhibited significant potent activity against TOP2α or TOP2A. This result indicated that the derivatives of Biginelli (3,4-dihydropyrimidinones/thiones) could be promising anti-prostate cancer drug candidates.

Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/β-catenin signaling pathway.

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.The canonical Wnt/β-catenin signaling pathway has been shown to be involved in the regulation of tumor proliferation, migration and differentiation. Activation of the canonical Wnt/β-Catenin signaling pathway in the prostate has oncogenic effects. Drugs targeting the canonical Wnt/β-catenin signaling pathway have great potential in the treatment of prostate cancer. In this study, we found that Gastrodin could significantly inhibit the proliferation of prostate cancer cell line PC3 and DU145. Oral administration Gastrodin could significantly inhibit the tumor growth of PC3 cells subcutaneously injected. Gastrodin has an inhibitory effect on canonical Wnt/β-Catenin signaling pathway in Prostate cancer, and this inhibitory effect can be abolished by Wnt/β-Catenin agonist LiCl. These findings raise the possibility that Gastrodin can be used in the treatment of Prostate cancer by targeting canonical Wnt/β-Catenin signaling pathway.

Double Hydroxyl Salt as Smart Biocompatible pH-Responsive Carrier for 6-Mercaptopurine

Hydroxy double salts are layered materials that are considered to be biocompatible. For this reason, research has been initiated on the possibility of their use in drug delivery. Despite their use for several types of drugs, their potential for controlled release of mercaptopurine (MERC) has not been studied. In this work, the synthesized hydroxy double salt (HDS) material was used as a carrier for this drug for the first time. The effectiveness of HDS synthesis has been proven by such techniques as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Based on the FT-IR and energy-dispersive X-ray spectroscopy (EDS) results, the effectiveness of drug sorption was proven. The exact amount of drug retained was determined by the UV-Vis technique. The obtained results indicate that the drug is evenly distributed on the surface of the carrier, which is important during the controlled delivery of drugs. In the most important stage of the research, the effectiveness of drug release in response to changes in the pH of the environment was proven. The drug is not released into an environment that mimics healthy human tissues. It is released only after contact with the acidic environment that usually surrounds cancer cells. The low cellular toxicity of HDS and significant cytotoxic effect of HDS-MERC were confirmed by in vitro studies on MCF-7 human breast and DU145 prostate cancer cell lines and non-cancerous keratinocytes HaCaT. Interestingly, coupling with the HDS carrier increased the cytotoxic effect of MERC towards DU145 cells. Such an “intelligent” drug carrier for mercaptopurine has not been previously described in the literature. The obtained results indicate its great potential.

Luteolin induces ferroptosis in prostate cancer cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

As the second most common cancer in men and the leading cause of cancer-related death, prostate cancer (PCa) could potentially be treated by inducing ferroptosis. In this study, we aimed to investigate whether luteolin could induce ferroptosis in PCa cells through the transcription Factor EB (TFEB). Different concentrations of luteolin were applied to treat normal prostate epithelial cells RWPE-1 and PCa cell lines DU145, PC-3, VCaP, and LNcaP. Ferrostatin-1 (Fer-1), Necrostain-1 (Nec-1), 3-methyladenine (3-MA), chloroquine (CQ), and the apoptosis inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK)were added to treat DU145 and PC-3 cells. Additionally, we knocked down TFEB and performed in vitro cell experiments. Finally, tumor-forming experiments in nude mice were conducted to verify luteolin mechanism in PCa after knocking down TFEB. There was no significant difference in RWPE-1 at 12, 24, and 48 h after treatment with 60 μM luteolin. However, a significant difference was observed between DU145 and PC-3 cells. Luteolin exhibited a promoting effect on PCa cell death. After treatment with luteolin, cell viability, and Ki67 expression were decreased, and AnV-PI-positive dead cells were increased. Fer-1, Nec-1, 3-MA, and Z-VAD-FMK reversed luteolin effects on DU145 and PC-3 cell viability, proliferation, and AnV-PI-positive dead cells. Among them, Fer-1 and 3-MA were more effective. Luteolin-induced increased autophagy and ferroptosis in DU145 and PC-3 cells. Moreover, luteolin promoted ferroptosis by inducing increased autophagy in DU145 and PC-3 cells. However, knockdown of TFEB reversed the ability of luteolin to induce lysosome degradation of ferritin. In addition, luteolin promoted PCa ferroptosis by inducing ferritinophagy in vivo. Luteolin-induced ferroptosis in PCa cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

Photoactivation of pheophorbide-a utilizing 670 nm LEDs elicits cancer suppressive effects in androgen-independent prostate cancer cellular models.

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the USA. Photodynamic therapy (PDT) is a state-of-the-art treatment that combines high selectivity with minor side effects. Pheophorbide-a (Pheo) is a natural pigment with a photosensitizer property. Our study delved into the impact of Pheo alone or Pheo-PDT combination on the androgen-independent metastatic prostate cancer (AIPC) cell lines DU-145 and C4-2. Furthermore, an in-depth examination has been conducted on the photocytotoxicity mechanism of Pheo-PDT in these specific cell lines. In vitro studies were conducted using the AIPC cell lines. DU-145 and C4-2 cells were treated with Pheo at different concentrations for 60 min alone, or Pheo treatment followed by exposure to 670 nm illumination (60 mW/cm2 in 88 s pulses), producing 5 J/cm2 via portable light-emitting diode. Our results show that Pheo-PDT substantially inhibits cell viability, anchorage-independent growth, and migration capacities and induces autophagy and apoptosis via the over-production of reactive oxygen species that mediates endoplasmic reticulum stress in AIPC cell lines. Our study highlights the potential benefits of Pheo-PDT in metastatic hormone-insensitive PCa cell lines. It paves the way for treating localized and locally advanced PCa as a possible candidate for castration-resistant prostate cancer.

Synthesis and Biological Evaluation of Some Novel 3,4-dichloroacetophenone Chalcones as Potential Antifungal, Anti Tubercular, and Cytotoxic Agents

Chalcones containing a variety of rings were found to possess significant biological activities including antibacterial, antifungal, anti-inflammatory, anticancer, anti-HIV, antimalarial, anthelmintic, MAO inhibition, and anti-angiogenic activities. The present study was to synthesize a series of novel 3,4-dichloro acetophenone derivatives including chalcones by Claisen-Schmidt condensation, to characterize the synthesized chalcones using suitable IR, 1H NMR, 13C NMR, mass spectra and elemental analyses data, to screen the synthesized chalcones for their antifungal, anti-tubercular, and cytotoxic activities, to identify the active compounds for further exploitation. The composition of the synthesized compounds was confirmed by elemental analysis and the results were also in close agreement with those of the calculated values. Results of the antifungal activity clearly notify that the chalcones exhibited significant antifungal activity with altered MIC values against the tested organisms, but not as much of the standard fluconazole. The results of the anti-tubercular activity of novel chalcones 3a-3o divulged that all the compounds exhibited considerable activity against the M. tuberculosis H37Rv strain. The titled compounds (3a-3o) were evaluated for their in vitro cytotoxic activity against prostate cancer cell line DU-145 by using MTT assay. Most potent chalcone of the series was 3o containing 2”-thienyl rings at portion-B, with an of MIC 5µg/mL which is equal to that of the positive control methotrexate.

Analysis of Quinolinequinone Analogs with Promising Cytotoxic Activity against Breast Cancer.

It is quite challenging to find out bioactive molecules in the vast chemical universe. Quinone moiety is a unique structure with a variety of biological properties, particularly in the treatment of cancer. In an effort to develop potent and secure antiproliferative lead compounds, five quinolinequinones (AQQ1-5) described previously have been selected and submitted to the National Cancer Institute (NCI) of Bethesda to envisage their antiproliferative profile based on the NCI Developmental Therapeutics Program. According to the preliminary in vitro single-dose anticancer screening, four of five quinolinequinones (AQQ2-5) were selected for five-dose screening and they displayed promising antiproliferative effects against several cancer types. All AQQs showed a excellent anticancer profile with low micromolar GI50 and TGI values against all leukemia cell lines, some non-small cell lung and ovarian cancer, most colon, melanoma, and renal cancer, and in addition to some breast cancer cell lines. AQQ2-5 reduced the proliferation of all leukemia cell lines at a single dose and five additional doses, as well as some non-small cell lung and ovarian cancer, the majority of colon cancer, melanoma and renal cancer, and some breast cancer cell lines. This motivated us to use in vitro, in silico, and in vivo technologies to further investigate their mode of action. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ3, in HCT-116 colon cancer, MCF7 and T-47D breast cancer, and DU-145 prostate cancer cell lines, and HaCaT human keratinocytes. Concomitantly, IC50 values of AQQ2 and AAQ3 against MCF7 and T-47D cell lines of breast cancer, DU-145 cell lines of prostate cancer, HCT-116 cell lines of colon cancer, and HaCaT human keratinocytes were determined. AQQ2 exhibited anticancer activity through the induction of apoptosis and caused alterations in the cell cycle. In silico pharmacokinetic studies of all analogs have been carried out against ATR, CHK1, WEE1, CDK1, and CDK2. In addition to this, in vitro ADME and in vivo pharmacokinetic profiling for the most effective AAQ (AAQ2) have been studied.

Berbamine Inhibits the Biological Activities of Prostate Cancer Cells by Modulating the ROS/NF-κB Axis.

This study aimed to explore the mechanism of berbamine in inhibiting prostate cancer. Prostate cancer cell lines PC-3 and DU145 cells were used to evaluate the effects of berbamine. Cell viability was determined using cell-counting kit 8. The intracellular reactive oxygen species (ROS) levels were measured using a ROS assay kit. Cell apoptosis rate was examined using flow cytometry. The protein levels associated with cell proliferation, NF-κB pathway, and apoptosis were determined using western blot. It was found that berbamine induced cell cycle arrest in the S phase and inhibited prostate cancer cell growth and proliferation. Berbamine inhibited prostate cancer cells by inhibiting the activation of the NF-κB pathway in vitro. Berbamine increased ROS as an upstream molecule that inhibited the NF-κB pathway. Our results demonstrated that berbamine can effectively reduce the proliferation of prostate cancer cells. The ROS/NF-κB axis plays a crucial role in berbamine-mediated anti-prostate cancer cell proliferation.

LC-MS metabolomic evidence metabolites from Oenothera rosea L´ Hér. ex Ait with antiproliferative properties on DU145 human prostate cancer cell line

Prostate cancer remains one of the leading health issues without a fully effective treatment. Medicinal plants are one of the primary sources of compounds for treating numerous ailments. In this sense, the Oenothera genus contains metabolites with antiproliferative activity on cancer cells. For this, the study aimed to explore the antiproliferative activity of its extracts against prostate cancer and identify its metabolites (under metabolomics analyses) associated with anticancer and/or antiproliferative properties. For this reason, a LC-MS/MS-based metabolomic analysis was performed to demonstrate the possible metabolites present in O. rosea. In addition, the antiproliferative activity of different extracts in the human prostate cancer cell line DU145 was evaluated. All extracts have antiproliferative effects on DU145 cells at 72 h, with moderate activity being the best ethanolic either 48 or 72 h. Finally, by LC-MS/MS-based metabolomics, 307 compounds from aqueous, methanolic, ethanolic, and ethyl acetate extracts from which 40 putative metabolites identified were organized as anti-inflammatory, anticancer, and/or antiproliferative activities according to previously reported. These results provide evidence that O. rosea could be used as an antiproliferative agent due to its chemical contents used as polypharmacy with low concentration levels.

The cytotoxic and apoptotic effects of $\textit{Abies nordmanniana subsp. bornmülleriana Mattf }$ resin extract on prostate cancer cell cells

Cancer has become one of the most critical health issues, with an increasing incidence and mortality in recent years. Meanwhile, many studies are carried out on discovering new compounds which reflects effective results on cancer cells. Therefore, this study aimed to examine the cytotoxic, anti-proliferative and apoptotic effects on cancer cell lines by using the extract obtained from Uludağ Fir ($\textit{Abies nordmanniana subsp. bornmülleriana Mattf }$) resin. Uludağ Fir resin extract was obtained by applying the methanol extraction method. In our study, fibroblast cell L-929, human metastatic prostate cancer PC-3 and human metastatic prostate cancer DU-145 cell lines were cultured in RPMI-1640 medium. The effects of the resin extract concentrations on the viability of the cells were determined with the Muse™ Cell Count & Viability test. In addition, apoptosis and cell cycle phases of the cells were determined using the Muse™ cell analyzer. Finally, RT-qPCR analysis was performed to determine the resin extract effect on pro-apoptotic and anti-apoptotic gene expression. The apoptotic effect of Uludağ Fir resin extract on cancer cell lines was significantly higher in contrast to the healthy normal cells. In addition, it was determined that Uludağ Fir extract caused G0/G1 cell cycle arrest in cancer cells. In RT-qPCR analysis, the pro-apoptotic gene expression levels were apparently increased in cancer cells, which was followed by a decrease in the anti-apoptotic gene expression levels. All taken together, these results indicate that Uludağ Fir resin extract exerts two prong effects as it induces a cell cycle arrest and apoptotic pathway activation on human prostate cancer cell lines.