Breast Cancer Cells Research Articles

Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types.

Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC's mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies.

Pan-cancer analysis of phagocytosis regulators in female-specific cancers: a focus on HMGB2

IntroductionTumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment, regulating immune escape and promoting cancer progression. Understanding the role of phagocytosis regulators in female-specific cancers is essential for developing effective therapeutic strategies.MethodsWe performed comprehensive analyses of public databases to evaluate the expression, somatic mutations, and copy number variations of phagocytosis regulators. DNA methylation patterns, biological pathways, survival outcomes, and drug sensitivity were assessed. Additionally, immune modulators, immune cell infiltration, and single-cell sequencing were used to explore alterations in phagocytosis and their cellular origins. The functional role of HMGB2 in tumor cell behavior was validated through in vitro assays.ResultsPhagocytosis regulators exhibited differential expression across various female-specific cancers, with key genes such as CD47 and FOXO1 playing significant roles in modulating tumor progression. High-frequency mutations were found in PTEN, ARID1A, and UBR4. Genes like COX5B and MS4A1 emerged as potential predictors of clinical outcomes and therapeutic response. HMGB2 knockdown significantly inhibited cancer cell proliferation, migration, and invasion in female-specific cancers. HMGB2 knockdown in macrophages led to a significant impairment in phagocytosis of breast, cervical, ovarian, and endometrial cancer cells. Furthermore, when HMGB2 knockdown was combined with Palbociclib treatment, a significant decrease in tumor cell proliferation was observed across multiple cancer models.ConclusionThis study highlights the pivotal role of phagocytosis regulators, particularly HMGB2, in the progression of female-specific cancers. Targeting HMGB2 offers promising therapeutic opportunities, potentially enhancing precision oncology and improving patient outcomes.

NEDD4 signaling: a new frontier in the diagnosis and treatment of breast and ovarian cancers.

Currently, breast cancer (BC) and ovarian cancer (OC) are the most prevalent forms of cancer among women worldwide. Even though BC has a favorable outlook when detected early and managed appropriately compared to OC, the spread of BC and OC to other parts of the body, known as metastasis, is a significant cause of death. A robust association exists between genetic and protein alterations and post-translational modifications (PTMs), significantly impacting tumor formation, advancement, and prognosis. Ubiquitination, a crucial PTM, regulates almost all aspects of cellular function, and E3-ligase-mediated ubiquitination is a pivotal process that controls the speed of the protein ubiquitination cascade. NEDD4-1, a neural developmentally downregulated protein 4-1, is a crucial E3 ligase that plays a significant role in regulating several proteins that have important functions in the development and progression of BC and OC, thus controlling BC and OC cells' movement, infiltration, and multiplication. This review discusses the latest developments in comprehending NEDD4-1 substrates and their involvement in signal transduction pathways in BC and OC. NEDD4-1 likely serves as a novel diagnostic indicator and a target for therapy in the battle against both cancers.

Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006).

GLP-1 receptor agonists (GLP-1 RA) are drugs used to treat diabetes by enhancing insulin sensitivity and secretion. Recent studies suggest their potential anti-cancer effects, including anti-inflammatory and antioxidant properties. This study evaluates the combined effects of GLP-1 RAs and radiotherapy (RT) on breast cancer progression in a BALB/c mouse model. In this study, BALB/c mice were injected with 4T1 breast cancer cells to induce tumors. The mice were randomly assigned to five groups: control, placebo, GLP-1 RA, RT, and combined GLP-1 RA with RT. Histological and immunohistochemical analyses were performed on the tumor tissues to assess changes in morphology and protein expression related to inflammation and apoptosis. In vitro, cell viability assays were also conducted on 4T1 cells to evaluate the effects of GLP-1 RA and RT. The combination of GLP-1 RA and RT resulted in significant tumor size reduction compared to the other treatment groups. Histological analysis showed improved tissue morphology, with restored healthy appearance in tumors treated with both GLP-1 RA and radiotherapy. Immunohistochemical staining revealed changes in the expression of apoptosis-related proteins. In vitro assays demonstrated that the combined treatment significantly decreased the viability of 4T1 breast cancer cells. This study concludes that the GLP-1 RAs and RT combination enhances tumor control and improves histological outcomes in a breast cancer model. This approach offers a promising strategy for patients with coexisting diabetes and breast cancer, potentially improving treatment efficacy and patient outcomes.

Exploring Antibacterial, Antioxidant, Cytotoxic Potential of Oscillatoria sp.-Derived Metabolites and Their Molecular Docking with Estrogen Receptor-α.

Anthropogenic activities have led to the accumulation of carcinogenic toxicants in the food chain, posing severe risks to both human and animal health. Bioactive molecules derived from terrestrial and aquatic systems offer promising solutions to various health challenges. Presently, the cyanobacterial metabolites from ethyl acetate extract of Oscillatoria sp. (EAEOs) were evaluated for its antiproliferative, antioxidant, and antimicrobial effects. The EAEOs resulted significant antibacterial zones (12 ± 2.5, 17 ± 1.7, 14 ± 0.3, and 14 ± 2.6mm) on Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Bacillus cereus, respectively. EAEOs also exhibited free radical scavenging activity with IC50 values of 69.68µg/mL (DPPH) and 144.4µg/mL (hydroxyl radicals). Followed by, the EAEOs also exhibited significant inhibition of MCF-7 breast cancer cells (IC50: 54.25µg/mL) compared to HepG2 and A549 cells (72.6 and 85.6µg/mL), respectively The EAEOs induced apoptosis and chromosomal damage on targeted cancer cells, and their DNA fragmentation were evidenced. Totally, 17 compounds from EAEOs were identified from GC-MS, in which 2-cyclopenten-1-one, 2-hydroxy-3-methyl (23); piperidine, 1, 4-dimethyl (13); 17-pentatriacontene (7.88); and 3-octadecene (7.09%) are major ones. Molecular docking confirmed that acetamide, n-(2-benzoyl-4chlorophenyl)-2-(2-methylpiperidin-1-yl)- (compound-3) showed strong binding affinity (10.13kcal/mol) with ERα. Overall, the biological potential of Oscillatoria metabolites were found to be significant. Hence, further screening of preponderant compounds and studying the mechanism are warranted to fulfill their applications in food, pharmaceuticals, and other industries.

CD44 Receptor-Mediated Ferroptosis Induction by Hyaluronic Acid Carbon Quantum Dots in Triple-Negative Breast Cancer Cells Through Downregulation of SLC7A11 Pathway.

The field of cancer therapy is actively pursuing highly effective self-targeted drug delivery materials endowed with exceptional properties. Recently, hyaluronic acid (HA), a naturally occurring polysaccharide, has been recognized as a potential target ligand for CD44 receptors, which are frequently expressed on various solid tumor cells targeted in cancer therapy. HA carbon quantum dots (CQDs) exhibit several advantageous properties, including a high surface area-to-volume ratio, small particle size, biocompatibility, and low cytotoxicity, making them ideal for biomedical applications, such as CD44-targeted drug delivery in ferroptosis-based cancer therapy. In this study, we synthesized HA-CQDs to enhance CD44-mediated ligand-receptor interactions targeting triple-negative breast cancer (TNBC). CQDs facilitate the intracellular generation of reactive oxygen species (ROS), leading to glutathione depletion. These processes result in crucial actions such as the downregulation of glutathione peroxidase 4, downregulation of solute carrier family 7 member 11, and inhibition of cystine intake. The subsequent intracellular ROS, originating from lipid peroxidation, induces ferroptosis. Our HA-CQDs engage CD44 receptors, selectively targeting TNBCs and enhancing cancer recognition. This interaction potentially enhances the nanoplatform-based CD44 targeted therapeutic effects in inducing ferroptosis.

Novel Folate-Phenylfuran P-gp Inhibitor Conjugates for Overcoming Multidrug Resistance in MCF-7/ADR Cell.

P-glycoprotein (P-gp) functions as a critical membrane transporter that drives tumor resistance by mediating drug efflux, ultimately contributing to multidrug resistance (MDR). Recently potent inhibitors have shown significant potential in countering chemotherapeutic resistance, particularly in breast cancer. However, P-gp's presence in essential organs complicates clinical applications, underscoring the importance of developing tumor-specific targeting strategies. Given the high-level expression of folate receptors (FR) on the surface of breast cancer cells, this study conjugated a previously developed P-gp inhibitor with folic acid, with the goal of harnessing FR-mediated targeting for enhanced tumor cell specificity. In vitro evaluations reveal that the resultant conjugate maintains substantial resistance reversal efficacy against the MCF-7/ADR breast cancer-resistant cell line, comparable to the standalone inhibitor. The conjugate emerges as a highly potent and safe P-gp inhibitor in xenograft mouse, likely attributable to its enhanced tumor-targeting specificity, exhibiting superior in vivo efficacy when administered in combination with doxorubicin, relative to the original P-gp inhibitor.

Alginate and chitosan-coated ferulic acid-loaded selenium nanoparticles: synthesis, characterization, and anticancer activity against MDA-MB-231 breast cancer cells

Triple-negative breast cancer (TNBC), characterized by its aggressive behavior and lack of targeted therapies, remains a major therapeutic challenge. This study presents the synthesis and evaluation of ferulic acid-loaded selenium nanoparticles (FA-SeNPs) coated with alginate (Alg@FA-SeNPs) and chitosan (CS@FA-SeNPs) as potential nanocarriers for TNBC treatment. Ferulic acid was selected for its pro-apoptotic and anti-metastatic properties, despite its limited bioavailability. Encapsulation in SeNPs enhanced its stability and delivery efficiency. Alg@FA-SeNPs exhibited greater cytotoxicity (IC50: 103.6 µg/mL) than CS@FA-SeNPs (IC50: 178 µg/mL) after 48 h. Gene expression analyses showed significant H2AX upregulation with Alg@FA-SeNPs, indicating genotoxic stress, and marked Bcl-2 downregulation with CS@FA-SeNPs, favoring apoptosis. Zeta potential measurements confirmed near-neutral surface charge for Alg@FA-SeNPs and strong positive charge for CS@FA-SeNPs, supporting good colloidal stability. These findings highlight the therapeutic promise of biopolymer-coated SeNPs, particularly alginate-coated formulations, as targeted drug delivery systems for TNBC.

Development and Characterization of Folic Acid‐Decorated Fucoidan‐Poloxamer 407 Self‐Assembled Nanogels Co‐Loading Curcumin and Paclitaxel for Synergistically Enhanced Chemotherapeutic Efficacy

ABSTRACTCancer‐targeted nanomedicines demonstrate considerable potential in anticancer treatment due to their unique properties that improve therapeutic efficiency while minimizing off‐target effects. In this research, curcumin (Cur) and paclitaxel (PTX) were co‐loaded into dual‐targeting folate receptor/P‐selectin nanocarriers, which were based on folate‐conjugated fucoidan‐poloxamer 407 copolymers (FA‐FP407), aiming to inhibit breast cancer through intravenous administration. The successful synthesis of the self‐assembled nanogels was confirmed by analyzing their chemical composition. The resulting nanogels exhibited optimal physicochemical properties, including a negative surface charge, spherical morphology, and a hydrodynamic diameter of 158.27 ± 3.15 nm, along with high drug‐loading efficiency. The in vitro drug release from the nanogels significantly accelerated within the tumor microenvironment at pH 5.5, while it slowed down under physiological conditions. The drug release kinetics adhered to a Fickian diffusion model. Additionally, the blank nanocarriers were both hemocompatible and cytocompatible, although they exhibited slight growth inhibition of MCF‐7 breast cancer cells. FA‐FP407@Cur@PTX demonstrated a lower IC50 compared to both free drug formulations and single drug‐loaded nanogels in MCF‐7 cells, indicating that FA‐FP407@Cur@PTX nanogels could enhance anticancer activity by co‐administering different drugs and precisely accumulating drugs at the cancerous site. This effect is attributed to strong synergistic actions and receptor‐mediated cellular uptake. This study provides a solid foundation for advancing targeted nanomedicine, facilitating the co‐delivery of multiple therapeutic agents to achieve superior synergistic effects in chemotherapy.

Tubeimoside I inhibits the growth of triple-negative breast cancer via the NR3 C2/PI3 K/AKT signaling pathway.

Tubeimoside I (TBMS1) is a natural triterpenoid saponin extracted from the rhizome of Bolbostemma paniculatum and has been proven to be an effective antitumor agent for the treatment of various human cancers. In this study, we used a comprehensive approach involving bioinformatics analysis and in vivo and in vitro experiments to investigate the effects of TBMS1 on triple-negative breast cancer (TNBC) cells and elucidate the underlying molecular mechanisms involved. In vitro experiments revealed a dose-dependent decrease in the growth, movement, and infiltration of MDA-MB-231 and MDA-MB-468 cells due to TBMS1. A greater increase in the TBMS1 concentration (0, 7.58, and 15.16μM) was associated with a greater decrease. The flow cytometry results indicated that TBMS1 promoted apoptosis and induced cell cycle arrest in TNBC cells. The immunoblotting and NR3C2 gene knockdown results suggested that the inhibitory effect of TBMS1 on TNBC may be mediated via the NR3C2/PI3K/AKT signaling pathway. Comprehensive bioinformatics analysis was used to dissect the mechanism underlying the action of TBMS1 in TNBC cells at the molecular level. In the in vivo experiments, we established subcutaneous tumor xenograft models in female BALB/c mice, confirming the notable antitumor activity of TBMS1. The findings of our study demonstrate that TBMS1 significantly inhibits TNBC via the NR3C2/PI3K/AKT signaling pathway, suggesting that TBMS1 could be a potential tumor inhibitor.

Retraction: Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

Retraction: Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

DNMT3A facilitates breast cancer progression via regulating ADAMTS8 mediated EGFR-MEK-ERK activation.

ADAMTS8 inactivation by epigenetic modifications has been reported in various tumors, and the dysregulation of ADAMTS8 expression is associated with poor clinical outcomes, cancer cell invasion, and metastasis. De novo methylation, involving DNMT3A, plays an important role in cancer development; however, it remains unclear whether DNMT3A regulates the progressive expression of breast cancer by regulating ADAMTS8. Through published cancer-related datasets and clinical validation, we found that ADAMTS8 and DNMT3A expression negatively correlated in breast cancer, and both associated with patient prognosis. Related cell experiments have shown that DNMT3A overexpression promotes breast cancer cell proliferation, migration, invasion, and apoptosis, whereas silencing DNMT3A has the opposite effect. Through Co-IP experiments, we confirmed that DNMT3A binds directly to ADAMTS8. Methylation-specific PCR (MSP) experiments confirmed that DNMT3A mediates ADAMTS8 promoter methylation in breast cancer. In addition, DNMT3A activated the EGFR-MEK-ERK signaling pathway by effectively downregulating ADAMTS8, whereas silencing ADAMTS8 effectively inhibited this signaling pathway. Taken together, our findings suggest that DNMT3A activates the EGFR-MEK-ERK signaling pathway by silencing ADAMTS8 transcription through methylation, thereby promoting breast cancer development. Therefore, DNMT3A may serve as an inhibitory target in breast cancer-targeted therapy.

Comparative evaluation of immunomodulatory cytokines for oncolytic therapy based on a high-efficient platform for oHSV1 reconstruction

BackgroundTriple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its immunosuppressive tumor microenvironment (TME). Oncolytic herpes simplex virus type 1 (oHSV1) offers dual mechanisms of tumor lysis and immune activation, yet the optimal cytokine payloads for TNBC remain undefined.MethodsWe developed a CRISPR/Cas9-mediated platform for high-efficiency oHSV1 engineering, replacing the ICP47 locus with murine IFN-γ, GM-CSF, or IL-15Rα/IL-15 fusion protein (IL15Fu). Constructs were validated for cytokine secretion, MHC modulation, and cytotoxicity in 4T1 TNBC and a panel of human cancer cell lines. Antitumor efficacy and immune remodeling were evaluated in a syngeneic 4T1 model using RNA sequencing and flow cytometry.ResultsThe CRISPR platform achieved 62.5–71.4% homologous recombination efficiency, enabling rapid virus construction. In vitro, OV-IFNG exhibited upregulated MHC I/II expression and potent cytotoxicity, while OV-GMCSF attenuated oncolysis in subsets of breast cancer cell lines. In the 4T1 model, OV-IL15Fu modestly improved tumor control and extended survival without apparent toxicity, while OV-IFNG induced early mortality associated with systemic toxicity. Transcriptomic profiling revealed divergent immune modulation: OV-IL15Fu enriched T cell/NK cytotoxicity pathways, OV-IFNG amplified cytokine/chemokine signaling, and OV-GMCSF paradoxically enhanced myeloid recruitment while inhibiting MHC-II pathways. Flow cytometry confirmed functional differences in immune activation: OV-IL15Fu expanding cytotoxic lymphocytes (CD8⁺ T/NK cells), OV-IFNG preferentially promote Th1 polarization and innate immune activation, and OV-GMCSF failed to activate T cells despite myeloid infiltration.ConclusionsOur findings underscore the need for rational cytokine selection in oHSV1-based immunotherapy. While IFN-γ increased immunogenic markers, its systemic toxicity and myeloid effects may limit benefit. GM-CSF exacerbated immune suppression in this context, whereas IL15Fu showed favorable immunostimulatory properties without detectable toxicity. These data support IL15Fu as a contextually promising payload for further evaluation in TNBC-targeted oncolytic virotherapy.

Rewired glycolysis by DTL accelerates oncometabolite L-lactate generation to promote breast cancer progression

Breast cancer (BC) has become the leading cause of global cancer incidence. Despite therapeutic advances, a critical unmet need persists for identifying novel therapeutic targets. Our integrated bioinformatics analysis identified DTL, a component of the Cullin-RING ligase (CRL) E3 ubiquitin ligase family, as significantly upregulated in BC tissues. This upregulation correlated with poor patient prognosis, cancer stemness, and metabolic reprogramming, which was driven by genetic alterations such as gene amplification and reduced promoter methylation. Functional studies demonstrated that DTL promoted breast cancer cell proliferation and migration in vitro through glycolysis remodeling. Mechanistically, DTL positively regulated key glycolytic enzymes (HK2, ENO1, PKM2, and LDHA) independently of its canonical ubiquitin ligase activity and directly interacted with LDHA. Notably, exogenous L-lactate directly enhanced BC tumor growth and metastasis. Collectively, our findings reveal a non-canonical mechanism whereby DTL drives glycolysis to generate the oncometabolite L-lactate, which directly sustains breast cancer malignancy independent of protein degradation. The strong association between DTL upregulation and adverse clinical outcomes, coupled with its multifaceted regulatory roles in tumor biology, highlighting its therapeutic potential as a novel target in BC.

Exosomal miR-122-5p for regulation of secretory functions of fibroblasts and promotion of breast cancer metastasis by targeting MKP-2: an experimental study

ABSTRACT Tumor metastasis is a major obstacle for the effective treatment of breast cancer. Some studies showed that exosomes could promote tumor distant metastasis by establishing pre-metastasis niches (PMN). MicroRNAs (miRNAs) in exosomes play a critical role in tumor development and invasion. We aimed to investigate the effects of exosomal miRNAs derived from breast cancer cells on metastasis. MiRNA sequencing and RT-PCR approach were used to screen potential exosomal miRNAs. We compared the levels of serum exosomal miRNAs from breast cancer patients and those from MCF10A/MCF7/MDA-MB-231 cells. We found that differential exosomal miRNAs screened from patients with metastasis have higher expression levels in exosomes secreted by MDA-MB-231 cells. Using miRNA mimics or inhibitors, exosomal miR-122-5p was found to enhance the secretion levels of chemokine MCP-1 and SDF-1 from WI-38 lung fibroblast cells. In vitro luciferase assay and western blot confirmed the targeting of 3’-untranslated region of MKP-2 and suppression of MKP-2 expression by miR-122-5p in WI-38 cells. Treatment of xenograft mice with exosomal miR-122-5p increased the levels of MCP-1 and SDF-1 in serum, and promoted lung metastasis of breast cancer. In conclusion, we identified exosomal miR-122-5p from breast cancer cells that could promote the chemokine secretion of lung fibroblasts, which might facilitate the chemotaxis and colonization of breast cancer cells in lung tissue.

Unraveling the Specific Recognition Between PD-L1 and Engineered CLP002 Functionalized Gold Nanostructures: MD Simulation Studies.

PD-L1 (programmed cell death ligand-1) is a protein located on the surface of regulatory cells. It has an immunosuppressive role as it binds specifically to the protein programmed cell death-1 (PD-1), a checkpoint glycoprotein, present on the surface of immune cells such as T and B lymphocytes. Many tumor cells block the immune response by overexpressing PD-L1 on their surface; therefore, targeting PD-L1 represents a powerful strategy that allows tumor localization. To determine the presence of PD-L1 in cells, the use of ad hoc functionalized peptides that bind to PD-L1 can be exploited. One of them is the peptide CLP002 (Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which, bound to surface-enhanced Raman scattering (SERS) gold nanostructures via a suitable linker, was shown to be highly effective in recognizing MDA-MB-231 breast cancer cells and, importantly, this recognition can be measured by SERS experiments. To characterize, on a molecular scale, the interaction between PD-L1 and peptide functionalized nanostructures, we performed molecular dynamics (MDs) simulations, studying the features of peptide monolayers bound on gold surfaces in the absence and presence of PD-L1. The results obtained allow us to explain why the nature of the linker plays a fundamental role in the binding and why a peptide carrying the same amino acids as CPL002 but with a different sequence (scrambled) is much less active than CLP002. These results open the way to an in silico evaluation of the key parameters that regulate the binding of PD-L1 useful for cancer recognition.

Systematic Review of the Antitumor Activities and Mechanisms of Scorpion Venom on Human Breast Cancer Cells Lines (In Vitro Study).

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide. Innovative therapies are essential to address its diverse subtypes and treatment resistance. Scorpion venom and its bioactive proteins have gained attention as potential anticancer agents owing to their multitargeted cellular effects. This review systematically evaluates their anticancer properties and mechanisms in breast cancer, highlighting therapeutic potential. Methods: A systematic search was conducted in five databases (PubMed, Science Direct, EMBASE, OVID, and KISS) up to September 2024. Only in vitro studies using breast cancer cell lines and investigating scorpion venom or its bioactive proteins were included. Extracted data covered study characteristics, intervention types, control groups, dose range, duration, and key outcomes. Results: In total, 19 studies met the eligibility criteria. Crude scorpion venom showed broad cytotoxicity against hormone receptor-positive, triple-negative, and HER2-positive breast cancer subtypes. The primary mechanisms included apoptosis induction, DNA fragmentation, oxidative stress modulation, and cell cycle regulation. Bioactive proteins, such as chlorotoxin (CTX) and Neopladine 1/2, exhibited selective anticancer effects by targeting signaling pathways, inhibiting migration and invasion, and promoting apoptosis. Conclusion: These findings support scorpion venom's potential as a multitargeted anticancer agent. The complementary actions of crude venom and its proteins highlight their promise for combination therapies. Further research is needed to clarify their synergistic interactions and optimize preclinical and clinical applications.

Cytotoxicity of L-asparaginase from eucaryotic Cladosporium species against breast and colon cancer in vitro

BackgroundRecent statistical analyses indicate a rapid increase in the incidence of breast and colon cancer in Egypt. Although invasive techniques have been widely employed for early detection, diagnosis, and intervention of those cancers, they are associated with inherent risks and limitations, which often result in various complications. Therefore, noninvasive screening methods are inevitable due to their accessibility, cost-effectiveness, and high patient compliance rates. The enzyme L-asparaginase catalyzes the conversion of L-asparagine to L-aspartic acid: key metabolite for tumor cell division, thereby demonstrating anticancer potential. However, the prolonged use of bacterial L-asparaginase may cause allergic reactions and side effects such as diabetes, leukopenia, and co-agglutination disorders. Exploring the anticancer properties of L-asparaginase from different species such as yeast and fungi has been proposed to mitigate these adverse effects.ObjectivesThis study aimed at extracting and optimizing the expression of L-asparaginase from the eukaryotic Cladosporium species, as to assess its anticancer potential against breast and colon cancer cell lines.MethodCladosporium species were identified morphologically and then cultured on modified Czapek-Dox Agar (mCDA) medium supplemented with L-asparagine to induce L-asparaginase production. Submerged fermentation was employed to optimize enzyme production. The enzyme activity was quantified using the Nesslerization method, and its cytotoxicity against colon and breast cancer cell lines was assessed using the (MTT) assay.ResultsAmong the Cladosporium isolates, 18.4% exhibited positive plate assay test, with enzyme activities ranging from 255 to 428 U/mL. Immunoblotting using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed single protein band of approximately 37 kDa, consistent with L-asparaginase activity. Cytotoxicity assay of purified L-asparaginase showed significant antiproliferative effects against breast cancer cell lines MCF-7 and MDA-MB-231, with IC50 values of 36.26 and 45.7 µg/mL, respectively.ConclusionCertain eukaryotic Cladosporium strains are potential sources for the anticancer L-asparaginase production.Graphical Microbial L-asparaginase is one of the most important industrial enzymes of interest accounting for about 40 % of the total worldwide enzyme sales, this enzyme has got much significance in the medical field for the treatment of leukemia especially acute lymphoblastic leukemia (ALL).

Breast cancer cell targeting of L-leucine-PLGA conjugated hybrid solid lipid nanoparticles of betulin via L-amino acid transport system-1

The aim of fabricating hybrid solid lipid nanoparticles (HSLN) was to enhance the delivery of betulin to triple negative beast cancer cells through the intravenous route via L-amino transporter system-1, using L-leucine-PLGA conjugate (Conj-HSLN) by hot high pressure homogenization method. Betulin (BN), having potent anticancer and antioxidant activity, faces challenges due to poor water solubility and permeability, affecting its bioavailability. The results revealed Conj-HSLN with particle size 318.3 ± 0.25 nm. The percent cumulative BN release from Conj-HSLN was 57.763%, 24h. The cytotoxicity study in MB-MDA-231 cell depicts, LD50 67.73 µg/ml in Conj-HSLN. Pharmacokinetics study reveals enhanced Cmax and half-life in Conj-HSLN (32.12 ± 0.25 µg/ml, 4.72 ± 0.53 h) than raw BN (1.31 ± 0.21 µg/ml, 7.54 ± 0.34 h). Enhanced distribution at tumor site (11.5967% ID, 2h) in Conj-HSLN signifies the role of L-leucine in the transport system. Pharmacodynamic study shows mean tumor volume of 765.3 ± 85.884, and 1450.01 ± 219.361 mm3 in Conj-HSLN, and BN respectively at 3rd week of treatment. Standardized uptake value attributed reduced glucose uptake, due to inhibited tumor growth and proliferation, confirmed tumor biomarkers assay, VEGF and Caspase-9. In conclusion, the targeted controlled release L-leucine conjugated-BN loaded HSLN is stable, safe, and effective against triple negative breast cancers.

ATPase copper transporting beta attenuates malignant features with high expression as an indicator of favorable prognosis in breast cancer.

ATPase copper transporting beta (ATP7B) functions as a copper-transporting ATPase that ejects copper from cells. Although high expression of ATP7B has been reported to increase cisplatin resistance, its role in breast cancer (BC) remains unclear. This study aimed to elucidate the function of ATP7B in BC cells and its significance in patients with BC. The mRNA and protein expression levels of ATP7B were evaluated in BC and non-cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between ATP7B and 84 cancer-related genes. ATP7B knockdown was performed using small interfering RNA, and cell proliferation, invasiveness, and migration were analyzed. The associations between the mRNA and protein expression of ATP7B and clinicopathological factors were also investigated in 156 patients with BC. ATP7B was found to be highly expressed in estrogen receptor-positive and human epidermal growth factor receptor 2-positive BC cell lines. PCR array analysis revealed a significant correlation between the expression level of ATP7B and those of cadherin 1, estrogen receptor 1, and MET proto-oncogene. ATP7B knockdown significantly increased the proliferation, invasiveness, and migration of MDA-MB-361 and MDA-MB-415 cells. Patients with high ATP7B expression at the mRNA and protein levels experienced favorable prognoses. In addition, ATP7B expression level was identified as an independent prognostic factor in multivariate analysis. ATP7B is involved in promoting anti-cancer activities of tumor suppressors in BC cells across different subtypes and is considered a prognostic marker for BC.