Search Results (6,122)

Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation. Full article

Background and Objectives: The cytokine IL-6, methyltransferase NSD2, pro-protein convertase Furin, and growth factor receptor IGF-1R are essential factors in the proliferation of cancer cells. These proteins are involved in the tumor process by generating several cell-signaling pathways. However, the interactions of these oncogenic biomarkers, Furin, IL-6, and NSD2, and their links with the inhibitor SERPINA-1 remain largely unknown. Materials and Methods: Cell proliferation is measured by colorimetric and enzymatic methods. The genetic expressions of SERPINA-1, Furin, IL-6, and NSD2 are measured by qRT-PCR, while the expression of IGF-1R on the cell surface is measured by flow cytometry. Results: The proliferation of cells overexpressing SERPINA-1 (JP7pSer+) is decreased by more than 90% compared to control cells (JP7pSer-). The kinetics of the gene expression ratios of Furin, IL-6, and NSD2 show an increase for 48 h, followed by a decrease after 72 h for the three biomarkers in JP7pSer+ cells compared to JP7pSer- cells. The expression of IGF-1R on the cell surface in both cell lines is low, with JP7pSer- cells expressing 1.33 times more IGF-1R than JP7pSer+ cells. Conclusions: These results suggest gene correlations of SERPINA-1 overexpression with decreased cell proliferation and modulation of gene expression of Furin, IL-6, and NSD2. This study should be complemented by molecular transcriptomic and proteomic experiments to better understand the interaction of SERPINA-1 with IL-6, Furin, and NSD2, and their effect on tumor progression. Full article

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, requiring innovative approaches to evaluate new therapies. Considering the high activity of unsymmetrical bisacridines (UAs) in PC monolayer cultures, we employed multicellular tumor spheroids (MCTS) to assess whether UAs retain pro-apoptotic activity under more physiologically relevant conditions. Ultra-low attachment plates were used to form spheroids from three PC cell lines (Panc-1, MIA PaCa-2, and AsPC-1) with different genotypes and phenotypes. The effects of UA derivatives (C-2028, C-2045, and C-2053) were evaluated using microscopy and flow cytometry (7-AAD for viability and annexin V-FITC/PI for membrane integrity). UAs altered the morphology of the spheroids and reduced their growth. Notably, Panc-1 spheroids exhibited compromised integrity. The increase in 7-AAD⁺ cells confirmed diminished cell viability, and annexin V-FITC assays showed apoptosis as the dominant death pathway. Interestingly, the exact derivative was most active against a given cell line regardless of culture conditions. These results confirm that UAs maintain anticancer activity in 3D cultures and induce apoptosis, with varying efficacy across different cell lines. This underscores the value of diverse cellular models in compound evaluation and supports UAs as promising candidates for pancreatic cancer therapy. Full article

Background/Objectives: Leukemia is associated with high recurrence rates and cancer vaccines are emerging as a promising immunotherapy against the disease. Here, we investigate the mechanism of action by which a personalized vaccine made from leukemia cells infected with an oncolytic virus (ICV) induces anti-tumor immunity. Methods: Using the L1210 murine model, leukemia cells were infected and irradiated to create the ICV. The CRISPR-Cas9 system was used to engineer knockout cells to test in treatment efficacy studies. Results: We found that pro-inflammatory interferons (IFNs) that are produced by infected vaccine cells induce the immunoproteasome (ImP), a specialized proteasome subtype that is found in immune cells. Interestingly, we show that while a vaccine using the oncolytic vesicular stomatitis virus (oVSV) completely protects against tumor challenge, the wild-type (wt) virus, which does not induce the ImP, is not as effective. To delineate the contribution of the ImP for vaccine efficacy, we generated ImP-knockout cell lines and found no differences in treatment efficacy compared to wild-type cells. Furthermore, an ICV using another murine leukemia model that expresses the ImP only when infected by an IFN gamma-encoding variant of the virus demonstrated similar efficacy as the parental virus. Conclusions: Taken together, our data show that ImP expression by vaccine cells was not required for the efficacy of leukemia ICVs. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

Cancer and infectious diseases are major causes of global morbidity and mortality stressing the need to find novel drugs with promising dual anticancer and antimicrobial efficacy. Gold complexes have been studied for the past years due to their anticancer properties, with a few of them displaying antimicrobial properties, which support their pharmacological interest. Within this scope, we investigated six gold bisdithiolate complexes [Au (bdt)₂]⁻ (1), [Au (dcbdt)₂]⁻ (2), [Au (3-cbdt)₂]⁻ (3), [Au (4-cbdt)₂]⁻ (4), [Au (pdt)₂]⁻ (5) and [Au (dcdmp)₂]⁻ (6), and) against the ovarian cancer cell lines A2780 and A2780cisR, the Gram-positive bacteria Staphylococcus aureus Newman, the Gram-negative bacteria Escherichia coli ATCC25922 and Burkholderia contaminans IST408, and the pathogenic yeasts Candida glabrata CBS138 and Candida albicans SC5134. Complexes 2 and 6, with ligands containing aromatic pyrazine or phenyl rings, substituted with two cyanonitrile groups, showed after 24 h of incubation high anticancer activities against A2780 ovarian cancer cells (IC₅₀~5 µM), being also able to overcome cisplatin resistance in A2780cisR cells. Both complexes induced the formation of ROS, activated caspase-3/7, and induced necrosis (LDH release) in a dose-dependent way, in a greater extent in the case of 6. Among the bacterial and fungal strains tested, only complex 6 presented antimicrobial activity against S. aureus Newman, indicating that this complex is a potential novel anticancer and antibacterial agent. These results delve into the structure-activity relationship of the complexes, considering molecular alterations such as replacing a phenyl group for a pyrazine group, and the inclusion of one or two cyanonitrile appendage groups, and their effects on biological activity. Overall, both complexes were found to be promising leads for the development of future anticancer drugs against low sensitive or cisplatin resistant tumors. Full article

Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article

The incidence and mortality of colorectal cancer (CRC) have increased globally. Several therapeutic approaches have been suggested to address this health issue, in addition to classical methods. Propranolol (PRO) is a beta-blocker that was repurposed to treat infantile hemangiomas, and its anti-tumor activity has been reported. This study aimed to investigate the effects of PRO in a panel of CRC cell lines and its potential impact when combined with chemotherapy. The effects of PRO on cell cytotoxicity, cell morphology, colony formation, cell death induction, cell cycle, mitochondrial and intracellular reactive oxygen species (ROS), and migration were measured in all cells. CompuSyn software was utilized to assess the possible synergistic or additive interaction in the combined treatment. The results showed that PRO suppressed cell proliferation, altered cell morphology, inhibited colony formation, induced apoptosis, altered cell cycle and ROS generation, and inhibited the migration of treated cells in a cell-type-specific, time-dependent, and dose-dependent manner compared with the control. HT-29 was the most sensitive cell line to PRO in terms of cytotoxicity, apoptosis, cell cycle arrest, and ROS generation, while SW-480 was the most sensitive in terms of migration inhibition. Moreover, the PRO and capecitabine combination exhibited a synergistic effect and induced mitochondrial apoptosis in metastatic CRC cells. The data suggest that PRO could be a promising adjuvant therapy for primary and advanced CRC. This study identified variations between CRC cell lines in response to PRO, which may be related to their genetic and epigenetic differences. In addition, the findings highlight the potential of combination strategies to improve therapeutic outcomes in metastatic CRC. Full article

Bifora testiculata (L.) Spreng. (Apiaceae), an understudied species endemic to the Mediterranean and the only representative species of the genus Bifora in Sicily, was investigated for the first time for its essential oil (EO) chemical composition and cytotoxic properties. The EO was obtained via hydrodistillation and analyzed using GC-MS, revealing an aldehyde-rich profile (86.10%), dominated by trans-2-dodecenal (67.49%). Comparative analysis with previous studies on B. testiculata from Greece confirmed a similar aldehyde-rich profile, although minor compositional differences suggest potential chemotype variation. Given the biological relevance of trans-2-dodecenal and related aldehydes, further investigations into the cytotoxic properties of the EO of B. testiculata (Bt) and its main constituent against cancer cell lines were undertaken. Three human tumor cell lines (MDA-MB 231, A375, and CaCo2) and a human non-tumor cell line (HEK293) were subjected to viability tests using the MTT assay. The EO and trans-2-dodecenal exhibited remarkable cytotoxic activity against all cell lines, with IC₅₀ values ranging between 7.93 and 14.41 µg/mL for Bt and between 1.88 and 5.29 µg/mL for trans-2-dodecenal. AO/BE fluorescent staining and Hoechst nuclear staining showed the presence of apoptotic bodies in the treated cells. N-acetyl-L-cysteine was able to invert the effects of Bt and trans-2-dodecenal on cell lines, suggesting ROS involvement in cytotoxic activity. The results demonstrated that the Bt cytotoxic activity was mainly due to the presence of trans-2-dodecenal. Full article

Annona amazonica R.E. Fries (synonyms Annona amazonica var. lancifolia R.E. Fries), popularly known in Brazil as “envireira”, is a tropical tree belonging to the Annonaceae family and is traditionally used as a food source. In this work, the in vitro and in vivo anti-liver cancer effects of essential oil (EO) from A. amazonica leaves were investigated for the first time. The chemical composition of the EO was evaluated via GC–MS and GC–FID. The alamar blue assay was used to evaluate the cytotoxicity of EOs against different cancerous and noncancerous cell lines. Cell cycle analyses, YO-PRO-1/PI staining, and rhodamine 123 staining were performed via flow cytometry in HepG2 cells treated with EO. The in vivo antitumor activity of EO was evaluated in NSG mice that were xenografted with HepG2 cells and treated with EO at a dose of 60 mg/kg. The major constituents (>5%) of the EO were (E)-caryophyllene (32.01%), 1,8-cineole (13.93%), α-copaene (7.77%), α-humulene (7.15%), and α-pinene (5.13%). EO increased apoptosis and proportionally decreased the number of viable HepG2 cells. The induction of DNA fragmentation and cell shrinkage together with a significant reduction in the ΔΨm in EO-treated HepG2 cells confirmed that EO can induce apoptosis. A significant 39.2% inhibition of tumor growth in vivo was detected in EO-treated animals. These data indicate the anti-liver cancer potential of EO from A. amazonica leaves. Full article

Prostate cancer (PCa) is the second leading cause of cancer-related death among men in most Western countries. Current therapies for PCa are limited, often ineffective, and associated with significant side effects. As a result, there is a growing interest in exploring new therapeutic agents, particularly from the polyphyletic group of algae, which offers a promising source of compounds with anticancer properties. Our research group has focused on investigating the effects of a novel oleoresin from Gracilaria chilensis, known as Gracilex^®, as a potential therapeutic agent against PCa using both in vitro and in vivo models. Our findings indicate that Gracilex^® exhibits a time- and dose-dependent inhibitory effect on cell survival in LNCaP and PC-3 PCa, reducing viability by over 50% and inducing apoptosis, as evidenced by a significant increase in activated caspase-3 expression in both cell lines. Moreover, Gracilex^® significantly reduces the proliferation rate of both LNCaP and PC-3 prostate cancer cell lines, as evidenced by a marked decrease in the growth curve slope (p = 0.0034 for LNCaP; p < 0.0001 for PC-3) and a 40–50% reduction in the proportion of Ki-67-positive PCa cells. In addition, Gracilex^® significantly reduces in vitro cell migration and invasion in LNCaP and PC-3 cell lines. Lastly, Gracilex^® inhibits tumor growth in an in vivo xenograft model, an effect that correlates with the reduced PCa cell proliferation observed in tumor tissue sections. Collectively, our data strongly support the broad antitumoral effects of Gracilex^® on PCa cells in vitro and in vivo. These findings advance our understanding of its potential therapeutic role in PCa and highlight the relevance of further investigating algae-derived compounds for cancer treatment. Full article

This study details how 3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one (3NPEO) behaves in terms of photophysics when exposed to different solvents. The solvatochromic effect study reveals significant polarity shifts in the excited states of the 3NPEO compound, likely due to an intramolecular proton transfer mechanism. Measurements of dipole moments provide insight into their resonance structures in both ground and excited states. Electrochemical analysis revealed a reversible redox process, indicating a favorable charge transport potential. HOMO and LUMO energies of the compound were computed via oxidation and reduction potential standards. 3NPEO exhibits optimal one-photon and two-photon absorption characteristics, validating its suitability for visible wavelength laser applications in photonic devices. Furthermore, molecular docking and dynamics simulations demonstrated strong interactions between 3NPEO and the progesterone receptor enzyme, supported by structure–activity relationship (SAR) analyses. In vitro cytotoxicity assays on the MDAMB-231 breast cancer cell line showed moderate tumor cell inhibitory activity. Apoptosis studies confirmed the induction of both early and late apoptosis. These findings suggest that 3NPEO holds promise as a potential anticancer agent targeting the progesterone receptor in breast cancer cells. Overall, the findings highlight the substantial influence of solvent polarity on the photophysical properties and the design of more effective and stable therapeutic agents. Full article

In this study, using 70% anhydrous ethanol as the extraction solvent, Moringa oleifera Lam. seed powder was extracted with the microwave-assisted extraction method, followed by purification using macroporous adsorbent resin NKA-9. The purified glucosinolate was subsequently hydrolyzed with myrosinase. The glucosinolate and its enzymatic product were identified as 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (4-RBMG) and benzyl isothiocyanate (BITC) by UV–Vis, FT-IR, NMR, and MS. The bioactivities, including anti-oxidation, anti-inflammation, and anti-tumor activities of 4-RBMG and BITC, were systematically evaluated and compared. The results show that at 5–20 mg/mL, the anti-oxidation effects of 4-RBMG on DPPH and ABTS free radicals are superior to those of BITC. However, at the same concentrations, BITC has stronger anti-inflammatory and anti-tumor activities compared to 4-RBMG. Notably, at a concentration of 6.25 μmol/L, BITC significantly inhibited NO production with an inhibitory rate of 96.67% without cytotoxicity. Additionally, at a concentration of 40 μmol/L, BITC exhibited excellent inhibitory effects on five tumor cell lines, with the cell inhibitory rates of leukemia HL-60, lung cancer A549, and hepatocellular carcinoma HepG2 exceeding 90%. This study provides some evidence that the enzymatic product, BITC, shows promise as a therapeutic agent for tumor suppression and inflammation reduction. Full article

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article