Inhibit Cancer Cell Growth Research Articles

Inhibition of NPC1 suppresses cell proliferation and β-catenin signaling activation of liver cancer.

Niemann-Pick Type C1 (NPC1) plays a significant role in the development of liver diseases and liver cancer. Our objective was to investigate the involvement of NPC1 in regulating liver cancer development. We observed that high levels of NPC1 expression in tumor tissues from patients with liver cancer were associated with a poor prognosis. Through in vitro experiments, we found that inhibiting NPC1 expression reduced the proliferation, invasion, and migration of liver cancer cells, while also inducing apoptosis in these cells. Additionally, the inhibition of NPC1 led to decreased activation of Wnt/β-catenin signaling. In vivo studies further supported our findings by demonstrating that the suppression of liver cancer cell growth was effectively achieved through the inhibition of NPC1. Overall, our results strongly indicate that the inhibition of NPC1 suppresses liver cancer cell proliferation. Targeting NPC1 is a promising potential therapeutic strategy for liver cancer.

Clinical functional proteomics of intercellular signalling in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has an atypical, highly stromal tumour microenvironment (TME) that profoundly contributes to its poor prognosis1. Here, to better understand the intercellular signalling between cancer and stromal cells directly in PDAC tumours, we developed a multidimensional proteomic strategy called TMEPro. We appliedTMEPro to profile the glycosylated secreted and plasma membrane proteome of 100 human pancreatic tissue samples to a great depth, define cell type origins and identify potential paracrine cross-talk, especially that mediated through tyrosine phosphorylation. Temporal dynamics during pancreatic tumour progression were investigated in a genetically engineered PDAC mouse model. Functionally, we revealed reciprocal signalling between stromal cells and cancer cells mediated by the stromal PDGFR-PTPN11-FOS signalling axis. Furthermore, we examined the generic shedding mechanism of plasma membrane proteins in PDAC tumours and revealed that matrix-metalloprotease-mediated shedding of the AXL receptor tyrosine kinase ectodomain provides an additional dimension of intercellular signalling regulation in the PDAC TME. Importantly, the level of shed AXL has a potential correlation with lymph node metastasis, and inhibition of AXL shedding and its kinase activity showed a substantial synergistic effect in inhibiting cancer cell growth. In summary, we provide TMEPro, a generically applicable clinical functional proteomic strategy, and a comprehensive resource for better understanding the PDAC TME and facilitating the discovery of new diagnostic and therapeutic targets.

Biological Characteristics of a Novel Bibenzyl Synthase (DoBS1) Gene from Dendrobium officinale Catalyzing Dihydroresveratrol Synthesis

Bibenzyl compounds are one of the most important bioactive components of natural medicine. However, Dendrobium officinale as a traditional herbal medicine is rich in bibenzyl compounds and performs functions such as acting as an antioxidant, inhibiting cancer cell growth, and assisting in neuro-protection. The biosynthesis of bibenzyl products is regulated by bibenzyl synthase (BBS). In this study, we have cloned the cDNA gene of the bibenzyl synthase (DoBS1) from D. officinale using PCR with degenerate primers, and we have identified a novel type III polyketide synthase (PKS) gene by phylogenetic analyses. In a series of perfect experiments, DoBS1 was expressed in Escherichia coli, purified and some catalytic properties of the recombinant protein were investigated. The molecular weight of the recombinant protein was verified to be approximately 42.7 kDa. An enzyme activity analysis indicated that the recombinant DoBS1-HisTag protein was capable of using 4-coumaryol-CoA and 3 malonyl-CoA as substrates for dihydroresveratrol (DHR) in vitro. The Vmax and Km of the recombinant protein for DHR were 3.57 ± 0.23 nmol·min−1·mg−1 and 0.30 ± 0.08 mmol, respectively. The present study provides further insights into the catalytic mechanism of the active site in the biosynthetic pathway for the catalytic production of dihydroresveratrol by bibenzylase in D. officinale. The results can be used to optimize a novel biosynthetic pathway for the industrial synthesis of DHR.

Repositioning of aripiprazole, an anti‑psychotic drug, to sensitize the chemotherapy of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited therapeutic options. Cisplatin is a primary chemotherapeutic agent utilized in combination with other drugs or radiotherapy for PDAC treatment. However, the severe side effects of cisplatin often necessitate discontinuation of therapy and drug resistance in tumor cells poses significant clinical challenges. Therefore, the development of effective therapeutic strategies is imperative. The present study investigated whether repositioning of the antipsychotic drug aripiprazole could sensitize the anticancer activity of cisplatin in pancreatic cancer at doses calculated by the combination index. The findings indicated that aripiprazole combined with cisplatin to suppress pancreatic cancer cell growth. Notably, the combination notably increased the expression of apoptosis markers, including cleaved caspase‑3, compared with cisplatin alone. Additionally, this combination effectively decreased XIAP and MCL‑1 expression via mitochondrial membrane potential change as revealed by JC‑1 assay, thereby inducing apoptosis. Furthermore, in fluid shear stress assay, the combination of aripiprazole and cisplatin notably inhibited cell adhesion and tumor spheroid formation. Mechanistically, phospho‑kinase array profiles showed that the enhanced anticancer efficacy of the combination treatment could be attributed to the inhibition of STAT3 signaling, which led to a significant reduction in tumor growth in a pancreatic cancer animal model. The results showed that the repositioning of aripiprazole inhibits cancer cell growth by blocking the STAT3 signaling pathway and effectively enhancing cisplatin‑induced apoptosis, thereby suggesting that the combination of aripiprazole and cisplatin may be a potent chemotherapeutic strategy for the treatment of pancreatic cancer.

Connexin 43 hemichannels and related diseases

Abstract Connexin 43 (Cx43) protein forms hemichannels (connexons) and gap junctions, with hemichannels consisting of six Cx43 molecules and gap junctions formed by two hemichannels. While gap junctions are prevalent in organs like the heart and liver, hemichannels are found in specific cell types, such as astrocytes and osteocytes. They allow the passage of small molecules (<1.5 kDa) between the cytoplasm and extracellular matrix. Cx43 hemichannels have emerged as potential therapeutic targets in various diseases, including central nervous system disorders, bone-related diseases, diabetic complications, wound healing, and cancers. Aberrant hemichannel opening can worsen conditions by releasing inflammatory elements, such as causing gliosis in neuronal cells. Conversely, functional hemichannels may inhibit cancer cell growth and metastasis. Recent studies are revealing new mechanisms of Cx43 hemichannels, broadening their therapeutic applications and highlighting the importance of regulating their activity for improved disease outcomes.

CSIG-21. THE ROLE OF GUT MICROBIOTA IN GLIOBLASTOMA: INSIGHTS FROM MICROBIOME-GENE EXPRESSION INTERACTIONS

Abstract Glioblastoma, the most aggressive form of primary brain tumor, remains a formidable clinical challenge due to its invasiveness and resistance to therapy. Emerging evidence suggests that the gut microbiome plays a crucial role in modulating cancer progression through complex interactions with host physiology. In this study, we investigated the influence of gut microbiota and tumor gene expression by analyzing stool and tissue samples from glioblastoma patients. Utilizing 16S rRNA sequencing of stool samples and NanoString gene expression analysis of tumor tissue samples, we explored the relationship between gut microbiome taxa and gene expression levels in tissue. Pathway analysis using KEGG and Gene Ontology databases was employed to elucidate the functional implications of these interactions. Our findings reveal contrasting effects of specific gut microbiota taxa and gene expression, with Fusobacterium demonstrating a potential oncogenic role, while Bifidobacteriaceae and Akkermansiaceae display potential tumor-suppressive effects. Fusobacterium is associated with the upregulation of key oncogenes and pathways promoting cancer cell survival, growth, and metabolism, whereas Bifidobacteriaceae and Akkermansiaceae are linked to the downregulation of genes involved in pathways promoting cancer cell survival and proliferation, such as MAPK signaling and stress response pathways, potentially inhibiting cancer cell growth. These results highlight the intricate interplay between gut microbiota composition and cancer biology and underscore the potential of gut microbiota modulation as a therapeutic strategy in glioblastoma management.

Effect of Acacia concinna Extract on Apoptosis Induction Associated with Endoplasmic Reticulum Stress and Modulated Intracellular Signaling Pathway in Human Colon HCT116 Cancer Cells.

Colorectal cancer (CRC) stands as one of the most prevalent cancer types and among the most frequent causes of cancer-related death globally. Acacia concinna (AC) is a medicinal and edible plant that exhibits a multitude of biological properties, including anticancer properties. This study aimed to investigate the impact of the AC extract on apoptosis induction and the underlying mechanisms associated with this effect in KRAS-mutated human colon HCT116 cells. The effect of AC extract on cell cytotoxicity was evaluated using MTT assay. Nuclear morphological changes were visualized with Hoechst 33342 staining, while mitochondrial membrane potential (MMP) was assessed via JC-1 staining. Flow cytometry was employed for cell cycle analysis, and intracellular ROS levels were determined using DCFH-DA staining. The results showed that HCT116 cells exposed to AC extract showed reduced cell growth and prompted apoptosis, as indicated by an increase in chromatin condensation, apoptotic bodies, the sub-G1 apoptotic cell population, and disrupted MMP. Expression levels of apoptosis mediator proteins determined by Western blot analysis showed an increase in pro-apoptotic proteins (Bak and Bax) while decreasing anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1), leading to caspase-7 activation and PARP inactivation. AC extract was also found to enhance intracellular reactive oxygen species (ROS) levels and stimulate endoplasmic reticulum (ER) stress. Furthermore, AC extract increases the phosphorylation of ERK1/2, p38, and c-Jun while downregulating PI3K, Akt, β-catenin, and their downstream target proteins. These results demonstrate that AC extract could inhibit cancer cell growth via ROS-induced ER stress associated with apoptosis and regulate the MAPK, PI3K/Akt, and Wnt/β-catenin signaling pathways in HCT116 cells. Therefore, AC extract may be a novel candidate for natural anticancer resources for colon cancer treatment.

Trichosanthin elicits antitumor activity via MICU3 mediated mitochondria calcium influx

IntroductionTrichosanthin (TK) is a glycoprotein extracted from the Chinese medicinal herb Trichosanthes kirilowi, which has anti-virus and anti-tumor activity. However, the target and detailed mechanism of TK remains elusive. ObjectivesWe aimed to identify novel antitumor targets of TK in lung adenocarcinoma and study its anti-tumor mechanism. MethodsWe utilized a Lewis lung carcinoma mouse model to evaluate the inhibition of TK on tumor growth. CCK8 assay was utilized to calculate IC50 of trichosanthin on A549 and H1299. In-vitro cellular assays and in-vivo xenograft mice studies were used to investigate MICU3 overexpression and TK treatment on tumor growth. Fluo-4 dye and JC-1 staining was used to measure the mitochondrial calcium levels and membrane potential. H&E and immunohistochemistry staining were applied the asses the effect of TK on tumor and microenvironment. RNA sequencing was applied to analyze transcriptome changes in TK-treated and MICU3-overexpressed tumor cells. The influence of trichosanthin on DNMT3B expression and MICU3 methylation were detected by qPCR and Western blotting. Transcriptional activity of the MICU3 gene was measured by ChIP-PCR and luciferase assays. ResultsTrichosanthin ihibited the tumor growth in vivo, resulting cancer cell growth inhibition and cell death, with almost no effect on normal cells. IC50 of trichosanthin in A549 and H1299 cells were 62.8 μg/ml and 39.7 μg/ml, respectively. Mitochondrial Calcium Uptake Family complex MICU3 was shown to associated with favorable prognosis and was upregulated upon trichosanthin treatment, along with reduces tumor cell growth and migration, and increased cell death both in vitro and in vivo. Increased mitochondrial calcium level was observed in MICU3 overexpression cells. Pathway analysis of RNA-seq data revealed that cytokine and receptor pathways were enriched in MICU3-overexpressing cells. Trichosanthin decreased DNMT3B expression and altered MICU3 methylation while increased FOSL2 expression and reduced methylation that correlated with increased transcription of the MICU3 gene. ConclusionTrichosanthin elicits antitumor activity in lung adenocarcinoma via repressing DNMT3B and increasing FOSL2, which in turn induces MICU3-mediated mitochondrial calcium influx and tumor cell death.

Anticancer Potential of Cyanidin and Cyanidin-3-Glucoside Through TrkB Receptor Inhibition: Evidence From Molecular Interaction Docking

Cancer remains a global health problem with persisten demand on therapeutic development to inhibit cancer cells growth without harmful effects on healthy cells. Plant bioactive compounds are intensively studied as anticancer via several signalling pathway. Anticancer therapy via inhibition of tropomyosin kinase receptor-B (TrkB) signal was previously proposed as target therapy. The role of plant metabolites cyanidin and cyanidin-3-glucoside as TrkB inhibitor is has not been investigated. This study was aimed to identify physicochemical of cyanidin and cyanidin- 3-glucoside as well as determine it’s role towards TrkB receptor signalling pathway through in silico approach. Molecular docking was performed using Hex 8.0.0 software and visualizes using Discovery Studio Visualizer. The energy binding of TrkB with cyanidin and cyanidin-3-glucoside was -263,21 kcal/mol and 281,65 kcal/mol respectively. Complex of cyanidin-3-glucoside had hydrogen and hydrophobic bond more than TrkB-cyanidin complex. The hydrogen bond formed at Lys637, Arg558 and Gly 561 amino residues. Physicochemical analysis demonstrated that both ligand are potential as kinase enzyme inhibitor. Cyanidin-3-glucoside was predicted more potential as anticancer than cyanidin via TrkB receptor inhibition. Future studies are required to confirm current finding both in-vitro and in-vivo models.

PreMLS: The undersampling technique based on ClusterCentroids to predict multiple lysine sites.

The translated protein undergoes a specific modification process, which involves the formation of covalent bonds on lysine residues and the attachment of small chemical moieties. The protein's fundamental physicochemical properties undergo a significant alteration. The change significantly alters the proteins' 3D structure and activity, enabling them to modulate key physiological processes. The modulation encompasses inhibiting cancer cell growth, delaying ovarian aging, regulating metabolic diseases, and ameliorating depression. Consequently, the identification and comprehension of post-translational lysine modifications hold substantial value in the realms of biological research and drug development. Post-translational modifications (PTMs) at lysine (K) sites are among the most common protein modifications. However, research on K-PTMs has been largely centered on identifying individual modification types, with a relative scarcity of balanced data analysis techniques. In this study, a classification system is developed for the prediction of concurrent multiple modifications at a single lysine residue. Initially, a well-established multi-label position-specific triad amino acid propensity algorithm is utilized for feature encoding. Subsequently, PreMLS: a novel ClusterCentroids undersampling algorithm based on MiniBatchKmeans was introduced to eliminate redundant or similar major class samples, thereby mitigating the issue of class imbalance. A convolutional neural network architecture was specifically constructed for the analysis of biological sequences to predict multiple lysine modification sites. The model, evaluated through five-fold cross-validation and independent testing, was found to significantly outperform existing models such as iMul-kSite and predML-Site. The results presented here aid in prioritizing potential lysine modification sites, facilitating subsequent biological assays and advancing pharmaceutical research. To enhance accessibility, an open-access predictive script has been crafted for the multi-label predictive model developed in this study.

Synthesis of Black Seed Oil-loaded-, Alginate-based, pH-sensitive Beads Using Electrospraying Technique.

Black seed oil (BSO), derived from the seeds of the Nigella sativa plant, has garnered attention for its potential anti-cancer properties, particularly in the context of colon cancer. Its active compound, thymoquinone, may help inhibit cancer cell growth and induce apoptosis in colon cancer cells. Additionally, black seed oil's anti-inflammatory and antioxidant effects could contribute to a healthier gut environment, potentially reducing cancer risk. Therefore, this study synthesized pH-sensitive alginate beads to deliver BSO into the colon in a controlled-release manner without releasing the drug at pH 1.2 (stomach), thus providing a well-defined release pattern at pH 6.8. The use of electrospray technology improves process performance by making it easier to formulate small, homogeneous beads with a higher rate of swelling and diffusion in the gastrointestinal medium. The formulated beads were characterized by an ex-vivo mucoadhesive strength test, bead size, sphericity factor (SF), encapsulation efficiency (EE), scanning electron microscope (SEM), in vitro swelling behavior (SB), and in vitro drug release in acidic and buffer media. All these manufactured beads demonstrated modest sizes of 0.58 ± 0.01 mm and spherical shape of 0.03 ± 0.00 mm in this testing. The formulation showed promising floating and releasing properties in vitro. With a very low cumulative percentage of beads, the oil EE of 90.13% ± 0.93% was high, and the release study demonstrated more than 90% in pH 6.8 with good floating nature in the stomach. Additionally, the beads were evenly spaced throughout the intestine. The electrospraying approach used in this protocol can be reproducible, yielding consistent outcomes. Therefore, this protocol can be used for large-scale production for commercialization purposes.

Evaluating STING Agonist Impact on Kaposi’s Sarcoma-Associated Virus-related Cancers

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an etiological agent of multiple malignancies associated with compromised immunity, such as Kaposi’s sarcoma (KS) and Primary Effusion Lymphoma (PEL). KSHV infection is lifelong with no available treatment or vaccines and poses a high risk to immunocompromised individuals. The virus is transmitted via the oral and sexual route, and has a biphasic life cycle with a short lytic replication cycle followed by long-term latency, with the expression of few genes making detection difficult. Reactivation from latency results in a cascade of viral gene expression and pathogenesis. Critical to controlling KSHV infection is the cGAS-STING DNA-sensing pathway (STING), known to activate the type I interferon response and induce cancer cell death or growth inhibition. STING exhibits both anti-viral and anti-tumor responses, showing promise as a protein of interest to study for the development of a therapeutic treatment. By examining the in vitro effectiveness of STING agonists in inhibiting KSHV oncogenesis in PEL, the study aimed to provide the foundation for a potential novel therapeutic approach. Six patient-derived PEL cell lines were treated with the STING agonist diaminobenzamidazole (diABZI) in a dose-dependent manner. Four of the PEL cell lines exhibited decreased cell growth, viability, and colony formation, while two PEL cell lines were resistant to treatment, correlating with the presence or absence of STING expression. RNA-sequencing was performed and discovered upregulation of multiple interferon-stimulated genes (ISG) in responsive cell lines. Further investigations will explore STING agonists’ inhibition of PEL oncogenesis in vitro via colony formation and in vivo using a PEL xenograft model with NSG mice. Successful completion of this project will offer insight into potential clinical treatments for targeting KSHV infection and reactivation.

γ-Glutamylcyclotransferase is transcriptionally regulated by c-Jun and controls proliferation of glioblastoma stem cells through Notch1 levels.

Glioblastoma stem cells (GSCs) have been reported to cause poor prognosis of glioblastoma by contributing to therapy resistance. γ-Glutamylcyclotransferase (GGCT) is highly expressed in various cancer types, including glioblastoma, and its inhibition suppresses cancer cell growth. However, the mechanism of GGCT overexpression and its function in GSCs are unknown. In this study, we show that GGCT is highly expressed in GSCs established from a mouse glioblastoma model and its knockdown suppresses their proliferation. Effects of NRas and its downstream transcription factor c-Jun on GGCT expression were analyzed; NRas knockdown reduced c-Jun and GGCT expression. Knockdown of c-Jun also reduced expression levels of GGCT and inhibited cell proliferation. Consistent with this, pharmacological inhibition of c-Jun with SP600125 reduced GGCT and inhibited GSC proliferation. Furthermore, the GGCT promoter-reporter assay with mutagenesis demonstrated that c-Jun regulates the activity of the GGCT promoter via AP-1 consensus sequence. Gene expression analysis revealed that GGCT knockdown showed a repressive effect on the Delta-Notch pathway and decreased Notch1 expression. Notch1 knockdown alone inhibited the GSC proliferation, confirming that Notch1 is functional in this model. Forced expression of the Notch1 intracellular domain restored the growth inhibitory effect of GGCT knockdown. Moreover, GGCT knockdown inhibited GSC tumorigenic potential in vivo. These results indicate that GGCT, whose expression is promoted by c-Jun, plays an important role in the proliferation and tumorigenic potential of GSCs, and that the phenotype caused by its knockdown is contributed by a decrease in Notch1. Thus, GGCT may represent a novel therapeutic target for attacking GSCs.

Intrinsic Synergy and Selectivity for the Inhibition of Cancer Cell Growth Generated by a Polymer Ligand of Proximal Enzymes.

A fundamental understanding of the design of polymer ligands of proximal enzymes is essential for the precise targeting of cancer cells, but it is still in its infancy. In this study, we systematically investigated the contribution of the chain length, ligand density, and ligand ratio of proximal enzyme-targeted polymers to the efficacy, synergy, and selectivity for the inhibition of cancer cell proliferation. The results revealed that employing a moderate chain length as a scaffold allowed for an intrinsically high efficacy and synergy of proximal enzyme-targeted polymers, in contrast to single enzyme-targeted polymers that prefer longer chain length for efficacy. The synergy obtained in proximal enzyme targeting was not provided by the combination of the corresponding small molecules. Moreover, the maturation of the synergistic efficacy of the proximal enzyme-targeted polymers also improved selectivity. This study proposes a rational design for polymer inhibitors and/or ligands for cancer cells with a high efficacy and selectivity.

Integrative study to determine the anti-tumor role and mechanism of Chouchunpi San in colorectal cancer

IntroductionThe herbal formula Chouchunpi San (CCPS) is a traditional formula that has been widely used and proven effective in various clinical cancer treatments. However, the mechanism of its anticancer effect remains unclear. This study aims to determine the anti-tumor effect of CCPS on colorectal cancer (CRC) in vivo and in vitro and to explore the underlying molecular mechanisms. MethodsCell counting kit-8 assays, colony-forming assays, and flow cytometry for cell cycle and apoptosis assays were employed to determine the anti-tumor roles of CCPS. Liquid chromatography-mass spectrometry (LC-MS), network pharmacology, molecular docking, analysis of real-world clinical datasets of CRC, and western blotting were conducted to explore the molecular mechanism of CCPS on CRC. CRC xenografted mouse model, western blotting, and public CRC data analysis were conducted to evaluate the anti-tumor efficacy and mechanisms of CCPS on CRC. ResultsCCPS suppresses the growth of CRC cells and increases the number of apoptotic cells dose-dependently. CCPS targets and significantly downregulates RPA1 and enhances the phosphorylation of its downstream effectors, ATR and CHK1, which are critical for CRC progression. Additionally, CCPS shows a comparable anti-tumor effect in CRC xenografted mouse models compared to Capecitabine, a chemotherapy drug commonly used in clinics. DiscussionOur findings demonstrate the potential use of CCPS in cancer treatment by suppressing cancer cell growth and modulating the RPA1/ATR/CHK1 signaling pathway in CRC. Further investigations on the application of CCPS in cancer therapies could be extended to evaluate the potential in vivo toxicity and adverse events, as well as the synergistic effect of CCPS in combination with other chemotherapeutic agents.

Unveiling metabolo-genomic insights of potent antitumoral and antibiotic activity in Streptomyces sp. VB1 from Valparaíso Bay.

Streptomyces sp. VB1, an actinomycete isolated from marine sediments in Valparaíso Bay, Chile, synthesizes antimicrobial and antiproliferative compounds. This study presents comprehensive metabolomics and comparative genomics analyses of strain VB1. LC-HRMS dereplication and Molecular Networking analysis of crude extracts identified antibiotics such as globomycin and daunorubicin, along with known and potentially novel members of the arylomycin family. These compounds exhibit activity against a range of clinically relevant bacterial and cancer cell lines. Phylogenomic analysis underscores the uniqueness of strain VB1, suggesting it represents a novel taxon. Such uniqueness is further supported by its Biosynthetic Novelty Index (BiNI) and BiG-SCAPE analysis of Gene Cluster Families (GCFs). Notably, two Biosynthetic Gene Clusters (BGCs) were found to be unique to VB1 compared to closely related strains: BGC #15, which encodes potentially novel anthracycline compounds with cancer cell growth inhibition properties, and BGC #28, which features a non-canonical configuration combining arylomycin, globomycin, and siamycin BGCs. This supercluster, the first described to consist of more than two adjacent and functional BGCs, co-produces at least three antimicrobial compounds from different antibiotic families. These findings highlight Streptomyces sp. VB1's potential for discovering new bioactive molecules, positioning it as a promising candidate for further research.

Integrating computational methods and in vitro experimental validation reveals the pharmacological mechanism of Selaginella bryopteris (L.) Baker targeting major proteins in breast cancer

Breast cancer remains a significant global health challenge, necessitating the exploration of novel therapeutic options. The present study employs an integrated approach encompassing network pharmacology, molecular docking, molecular dynamics simulations, and in-vitro validation to investigate the potential of Selaginella bryopteris in breast cancer treatment. Initial network pharmacology analysis revealed different potential targets and pathways associated with breast cancer that could be modulated by S. bryopteris phytochemical constituents. Molecular docking and dynamics simulations further elucidated the stability and dynamics of protein-ligand complexes (lanaroflavone–EGFR and sequoiaflavone-CTNNB1). The in-vitro assays demonstrated the ability of S. bryopteris crude extract to inhibit cancer cell growth (IC50 - 78.34 μg/mL) migration and invasion, supporting the computational predictions. The integrated approach employed in the present study offers a robust framework for the systematic exploration of S. bryopteris in drug discovery as a promising candidate for breast cancer treatment.

The impact of Trifolium pratense extract on apoptosis and autophagy in NALM-6 cells: implications for B-ALL intervention.

B-cell acute lymphoblastic leukemia (B-ALL), a prevalent malignancy predominantly affecting children, poses challenges such as drug resistance and cytotoxicity despite available treatment methods. The persistence of these challenges underscores the necessity for innovative therapeutic approaches to enhance efficacy. Natural compounds derived from plants, recognized for their potential to inhibit cancer cell growth, have drawn attention. Trifolium pratense extract, known for its significant anticancer properties in previous studies, was the focus of this investigation. This experimental study aimed to explore the impact of T. pratense extract on apoptosis and autophagy in NALM-6 cells. The cells were exposed to varying concentrations of the extract at specific time intervals, with viability and metabolic activity assessed using Trypan blue exclusion and MTT assays. Flow cytometry was employed to evaluate apoptosis using Annexin V/PI staining and ROS production using DCFH-DA staining. Real-time PCR was used to quantify gene expression related to apoptosis, autophagy, and oxidative stress, with data analysis performed using GraphPad PRISM software. Trifolium pratense extract demonstrated the capacity to induce apoptosis, autophagy, and significantly increase ROS production in NALM-6 cells. These effects were facilitated by the upregulation of corresponding genes. The MTT assay revealed an IC50 of 231 μg/mL at 48 h, and Flow cytometry analysis showed a 51.8% increase in apoptosis in this cell line. Overall, this study emphasizes the effectiveness of T. pratense extract in inducing autophagy and apoptosis pathways in NALM-6 cells derived from B-cell acute lymphoblastic leukemia, suggesting its potential as a candidate for further investigation as a supplement in ALL treatment.

Abutilon indicum-mediated green synthesis of NiO and ZnO nanoparticles: Spectral profiling and anticancer potential against human cervical cancer for public health progression

BackgroundIntegrating nanomedicines for targeted cancer treatment and pursuing medicinally valuable components from nature are crucial for sustainable, potent alternatives to synthetic drugs in combating fatal diseases like cancer. Hence, a green synthesis of nickel oxide (NiO NPs) and zinc oxide nanoparticles (ZnO NPs) has been carried out by using the leaf extract of medicinally important plant Abutilonindicum. This sustainable approach to medical developments not only reduces the environmental effect of standard synthesis methods and offers new options for novel cancer therapeutics, but it also advances public health by using natural resources in a sustainable manner. MethodsThe synthesized nanoparticles were characterized by employing spectro-analytical techniques like UV–vis, FT-IR, SEM and powder XRD. Synthesized nanparticles were evaluated in the human cervical cancer cells (HeLa). ResultsNi-O stretching vibrations were observed at 402 cm−1, whereas that of Zn-O stretching was observed at 409 cm−1in the FT-IR spectrum, confirming the formation of nanoparticles. The XRD pattern revealed the crystallite size range of 1.35–2.84 nm for NiO NPs and 7.71–56.80 nm for ZnO NPs. The morphology of the nanoparticles, as indicated by the SEM images, was rod-like for NiO NPs and rock-shaped for ZnO NPs. Further, the cancer cell growth inhibition activity of the nanoparticles was examined by MTT assay against human cervical cancer cells (HeLa) proliferation and compared with cisplatin. MTT assay elucidated the significant anticancer efficacy of the synthesized nanoparticles, showcasing low IC50 values of 29±0.5 µg/ml for NiO NPs and 32±0.7 µg/ml for ZnO NPs. Furthermore, the anticancer activity of the NiO NPs was investigated using the Trypan blue dye exclusion technique, emphasizing the pronounced cytotoxic impact of NiO NPs on cancer cell viability. The outcomes underscore the notable anticancer properties of plant extract mediated metal nanoparticles as promising contenders for advancing cancer treatment modalities.

Effect of Beta Vulgaris Extract on the Michigan Cancer Foundation-7 (MCF-7) and Rat Embryo Fibroblast (REF)

The study aimed to study the cytotoxic effect of the aqueous extract of Beta vulgaris on the breast carcinoma cell MCF-7 and the normal cell REF. Six diluted concentrations of the aqueous extract of the plant roots including (7.8, 31.25, 62.5, 125, 250, 500) µg/ml, with three exposure periods of 24, 48, and 72 hrs. The quantitative estimation of the active compounds of the aqueous extract was calculated. It was found that the aqueous extract of plant contains many active compounds such as (tannins, phenols, flavonoids and glycosides). The effect of the extract on normal REF cells after an exposure period of 72 hrs, which is represented by the concentration that causes inhibition of the proliferation of normal REF cells by 50%, is (IC50) with the aqueous extract of B. vulgaris was (6.35) mg/ml. The aqueous extract of plant was tested to detect the cytotoxic effect of the aqueous extract and all concentrations used on the MCF-7 breast cancer cell. The results showed that increase in the percentage rate of inhibition of cancer cell growth was observed during the three exposure periods of 24, 48, and 72 hrs. There is significant differences at (p≤0.05) and compared with the control. The rate of inhibition ranges at the lowest concentration 500 µg/ml were (92.204±1.455) (93.616 ±1.376) and (95.325±1.407) respectively.