Inhibited Cancer Cell Migration Research Articles

Enhanced Antitumor Efficacy of Oncolytic Vaccinia Virus Therapy Through Keratin-Mediated Delivery in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) represents an aggressive subtype characterized by high rates of recurrence and metastasis, necessitating the exploration of alternative treatment strategies. Oncolytic vaccinia virus (OVV) therapy has emerged as a promising approach, selectively infecting and destroying tumor cells. However, its efficacy is often hampered by inadequate viral distribution within the tumor microenvironment. Here, we investigate the potential of keratin (KTN) as a carrier for OVV delivery to enhance viral distribution and antitumor efficacy. In vitro assays revealed that KTN significantly improves OVV stability, leading to increased tumor cell apoptosis and necrosis. Furthermore, KTN effectively inhibits cancer cell migration by suppressing the epithelial–mesenchymal transition (EMT) process and downregulating metastasis-related proteins. These findings are corroborated in a syngeneic TNBC mouse model, where KTN-mediated OVV delivery enhances cytotoxic T cell-mediated antitumor immune responses without compromising the anti-angiogenic effects of the virus. Notably, KTN alone exhibits antitumor effects by suppressing tumor growth and metastasis, underscoring its potential as a standalone therapeutic agent. In conclusion, our study underscores the promise of KTN-mediated OVV delivery as a promising therapeutic strategy for TNBC. By improving viral distribution, suppressing EMT, and enhancing antitumor immunity, this approach holds significant potential for enhancing patient outcomes in TNBC treatment. Further investigation is warranted to explore the broader utility of KTN in various cancer therapy approaches.

Covalent Inhibitors of S100A4 Block the Formation of a Pro-Metastasis Non-Muscle Myosin 2A Complex.

The S100 protein family functions as protein-protein interaction adaptors regulated by Ca2+ binding. Formation of various S100 complexes plays a central role in cell functions, from calcium homeostasis to cell signaling, and is implicated in cell growth, migration, and tumorigenesis. We established a suite of biochemical and cellular assays for small molecule screening based on known S100 protein-protein interactions. From 25 human S100 proteins, we focused our attention on S100A4 because of its well-established role in cancer progression and metastasizes by interacting with nonmuscle myosin II (NMII). We identified several potent and selective inhibitors of this interaction and established the covalent nature of binding, confirmed by mass spectrometry and crystal structures. 5b showed on-target activity in cells and inhibition of cancer cell migration. The identified S100A4 inhibitors can serve as a basis for the discovery of new cancer drugs operating via a novel mode of action.

Exploring Piperine: Unleashing the multifaceted potential of a phytochemical in cancer therapy.

Radiotherapy is a cornerstone in the treatment of solid tumors, with extensive Phase III trials confirming its effectiveness. As advancements in treatment technologies and our understanding of tumor resistance mechanisms continue, the role of radiation oncology is set to become even more pivotal. Addressing the global challenge of lethal cancers demands innovative strategies, particularly in minimizing the side effects associated with traditional chemotherapy and ionizing radiation (IR). Recently, there has been growing interest in natural compounds for radioprotection, aiming to prevent tumor development and metastasis. Piperine, a compound found in black and long pepper, has emerged as a promising chemopreventive agent that works effectively without harming normal cells. Mechanistically, piperine modulates key signaling pathways, inhibits cancer cell migration and invasion, and enhances sensitivity to IR. Combining piperine with radiotherapy offers a compelling approach, boosting treatment efficacy while protecting healthy tissues from radiation damage. Piperine's versatile role goes beyond radiosensitization to include radioprotection by inhibiting NF-κB activation, reducing autophagy, and promoting apoptosis in cancer cells. This dual action makes it a promising candidate for personalized cancer care. As research advances, the therapeutic potential of piperine may drive new frontiers in cancer treatment strategies.

Vitexin Inhibits TNBC Progression and Metastasis by Modulating Macrophage Polarization Through EGFR Signaling.

Triple-negative breast cancer (TNBC) lacks sensitivity to endocrine and targeted therapies, exhibiting high recurrence and poor prognosis postchemotherapy. Tumor-associated macrophages (TAMs) play a crucial role in cancer progression. Vitexin, a compound with diverse pharmacological effects including anti-cancer activity, remains unexplored in its impact on TAMs during TNBC development. This study aimed to investigate vitexin's effect on TNBC, its regulation of macrophage polarization (M1 vs. M2), and the underlying EGFR/PI3K/AKT/mTOR pathway. Our results demonstrated that vitexin suppressed the proliferation and invasion of TNBC cells (MDA-MB-231 and BT549) while inducing macrophage mediators that further inhibited cancer cell migration. Vitexin also promoted M1 polarization and suppressed M2 polarization, affecting EGFR phosphorylation and downstream signaling. In vivo, vitexin inhibited tumor growth, favoring M1 polarization and suppressing M2 polarization, with synergistic effects when combined with doxorubicin (Dox). These findings offer novel insights into vitexin's potential in TNBC treatment.

The Protective Potential of Butyrate against Colon Cancer Cell Migration and Invasion Is Critically Dependent on Cell Type.

Short-chain fatty acids such as butyrate are produced through the fermentation of dietary fiber by colonic bacteria. Preclinical studies indicate an anticancer potential of butyrate, but clinical evidence shows greater variability. The study hypothesizes the effectiveness of butyrate on reducing colon cancer cell migration and invasion may vary due to the cell-type. The study determines the efficacy of butyrate (0-4mM) to inhibit cancer cell migration, invasion, and related signaling proteins in three distinct human colorectal cancer (CRC) cell lines: HCT116, HT-29, and Caco-2.Butyrate exhibits a dose-dependent inhibitory effect on cancer cell migration and invasion. This inhibitory potential on oncogenic focal adhesion kinase (FAK) and sarcoma (Src) proteins is greater in HCT116 cells (1.1 and 0.8-fold) and HT-29 cells (0.9 and 0.4-fold) compared to Caco-2 cells, respectively. Conversely, E-cadherin protein, a classical epithelial cell marker and potential tumor suppressor, is 2.3-fold greater in HCT116 cells than in HT-29 cells and Caco-2 cells. Moreover, survival analysis from a public cancer database demonstrates that CRC patients with high E-cadherin expression have a 13% greater 5-year survival rate than those with low expression. Collectively, butyrate's anti-cancer efficacy on CRC cells varies depending on cell-type and is linked to the FAK/Src/E-cadherin pathway.

Exopolysaccharides from the Green Microalga Strain Coelastrella sp. BGV-Isolation, Characterization, and Assessment of Anticancer Potential.

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a new Bulgarian strain of the green microalga Coelastrella sp. BGV were investigated. A fast and convenient method of precipitation with cold ethanol was used to isolate EPS from the culture medium. The chemical characteristics of the isolated EPS were examined by colorimetric and spectrophotometric analyses, HPSEC-RID and HPLC-UV chromatography, and FT-IR spectroscopy. The results showed that the isolated EPS sample consists of three carbohydrate fractions with different molecular weights (11.5 × 104 Da, 30.7 × 104 Da, and 72.4 × 104 Da, respectively) and contains 7.14 (w/w%) protein. HPLC-UV analysis revealed the presence of galactose and fucose. The total uronic acid content in the sample was 4.5 (w/w%). The IR-FT spectrum of EPS revealed the presence of various functional groups typical of a polysaccharide (or proteoglycan) composed primarily of neutral sugars. The anticancer potential of the obtained EPS was assessed using cell lines with cancerous and non-cancerous origins as in vitro experimental models. The results of the performed MTT assay showed that EPS reduced the viability of the cervical and mammary carcinoma cell lines HeLa and MCF-7, while the control non-cancer cell lines BALB/3T3 and HaCaT were less affected. The HeLa cell line showed the highest sensitivity to the effects of EPS and was therefore used for further studies of its anticancer potential. The ability of EPS to inhibit cancer cell migration was demonstrated by wound-healing (scratch) assay. The cell cycle FACS analysis indicated that the EPS treatment induced significant increases in the sub G1 cell population and decreases of the percentages of cells in the G1, S, and G2-M phases, compared to the control. The fluorescent microscopy studies performed using three different staining methods in combination with Annexin V-FITC flow cytometric analysis clearly demonstrate the ability of EPS to induce cancer cell death via the apoptosis pathway. Moreover, an altered pattern and intensity of the immunocytochemical staining for the apoptosis- and proliferation-related proteins p53, bcl2, and Ki67 was detected in EPS-treated HeLa cancer cells as compared to the untreated controls. The obtained results characterize the new local strain of green microalgae Coelastrella sp. BGV as a producer of EPS with selective antitumor activity and provide an opportunity for further studies of its pharmacological and biotechnological potential.

Comprehensive Analysis of Berberis aristata DC. Bark Extracts: In Vitro and In Silico Evaluation of Bioaccessibility and Safety.

Berberine (BER) is an alkaloid found, together with other protoberberinoids (PROTBERs), in several species used in medicines and food supplements. While some herbal preparations containing BER and PROTBERs, such as Berberis aristata DC. bark extracts, have shown promising potential for human health, their safety has not been fully assessed. Recently, the EFSA issued a call for data to deepen the pharmacokinetic and pharmacodynamic understanding of products containing BER and PROTBERs and to comprehensively assess their safety, especially when used in food supplements. In this context, new data were collected in this work by assessing: (i) the phytochemical profile of 16 different commercial B. aristata dry extracts, which are among the most widely used preparations containing BER and PROTBERs in Europe; (ii) the In Vitro and In Silico investigation of the pharmacokinetic properties of BER and PROTBERs; (iii) the In Vitro cytotoxicity of selected extracts in different human cell lines, including tests on hepatic cells in the presence of CYP450 substrates; (iv) the effects of the extracts on cancer cell migration; and (v) the In Vitro molecular effects of extracts in non-cancer human cells. Results showed that commercial B. aristata extracts contain BER as the main constituent, with jatrorrhizine as main secondary PROTBER. BER and jatrorrhizine were found to have a good bioaccessibility rate, but they interact with P-gp. B. aristata extracts showed limited cytotoxicity and minimal interaction with CYP450 substrates. Furthermore, tested extracts demonstrated inhibition of cancer cell migration and were devoid of any pro-tumoral effects in normal cells. Overall, our work provides a valuable overview to better elucidate important concerns regarding botanicals containing BER and PROTBERs.

Therapeutic Insights into Low-intensity Vibration for Generating Induced Tumor-Suppressive Cells and Modulating the Bone Microenvironment

Bone frequently serves as a metastatic site for breast and prostate cancers. Given the potential of low-intensity vibration (LIV) to increase bone health and reduce cancer risk, this study investigated the impact of LIV on cancer cells, as well as noncancer cells such as lymphocytes and peripheral blood mononuclear cells (PBMCs). The results revealed that LIV exposure not only suppressed cancer cell migration but also triggered the generation of induced tumor-suppressing (iTS) cells. Conditioned medium (CM) derived from LIV-treated PBMCs shrank freshly isolated breast and prostate cancer tissues, and when CM was combined with a chemotherapeutic agent, additional antitumor effects were observed. Notably, iTS cell-derived CM hindered the maturation of the receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated bone-resorbing osteoclasts while promoting the differentiation of bone-forming osteoblasts. Intriguingly, the anticancer effects induced by LIV were replicated by simply shaking a cell-containing tube with a regular tube shaker. Using mass spectrometry-based proteomics, this study revealed enrichment of tumor-suppressing proteins, including enolase 1, moesin (MSN), and aldolase A (ALDOA), which are commonly found in oncogene-activated iTS cells, in LIV-induced CM. Sad1 and UNC-84 domain containing 1 (SUN1), a core component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, exhibited heightened expression, notably enhancing the response of lymphocytes to LIV. An ex vivo bone cancer model further demonstrated the potent anticancer effects of lymphocyte-derived CM. In conclusion, this study underscores the pivotal role of LIV in preventing bone loss in the tumor microenvironment.

Targeted Chemo-Phototherapy in Red Light with Novel Doxorubicin and Iron(III) Complex-Functionalized Gold Nanoconjugate (Dox-Fe@FA-AuNPs).

The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5±16.52 μg mL-1; MDA-MB-231: 112.0±12.31 μg mL-1; MDA-MB-231 (3D): 156.31±19.35 μg mL-1) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy.

JDF promotes the apoptosis of M2 macrophages and reduces epithelial-mesenchymal transition and migration of liver cancer cells by inhibiting CSF-1/PI3K/AKT signaling pathway

BackgroundThe interaction between cancer cells and the tumor microenvironment is of critical importance in liver cancer. Jiedu Granule formula (JDF) has been shown to minimize the risk of recurrence and metastasis following liver cancer resection. Investigating the mechanism underlying the therapeutic effects of JDF can extend its field of application and develop novel treatment approaches. MethodsWe established a rat liver orthotopic transplantation tumor model, and recorded the prognostic effects of JDF adjuvant therapy on the recurrence and metastasis of liver cancer. Liver and lung tissues were collected for immunofluorescence staining and H&E staining, respectively. In addition, THP-1 cells were incubated with PMA and IL-4 to induce them to differentiate into M2 macrophages. CSF-1 expression was knocked down using lentivirus to determine the function of CSF-1. Liver cancer cells were cultured with a conditioned medium (CM) or co-cultured with macrophages. Cell viability was determined using the MTT assay. The levels of CSF-1, CSF-1R, E-cadherin, N-cadherin, PI3K, AKT, and cleaved caspase-3 were detected using ELISA, Western blotting and qPCR. The ability of cells to migrate was assessed using cell scratch and transwell assays. Apoptosis was evaluated using flow cytometry. ResultsThe JDF treatment decreased the risk of liver cancer metastasis after surgery and the infiltration of CD206/CD68 cells in liver cancer tissue. In cell experiments, JDF showed effects in suppressing M2 macrophages activity and downregulating the expression of CSF-1 and CSF-1R. The concentration of CSF-1 in the supernatant was also lower in the JDF-treated group. Futhermore, M2-CM was found to promote cancer cell migration and epithelial-mesenchymal transition (EMT); however, these effects were weakened after administering JDF. Knocking down endogenous CSF-1 in M2 macrophages resulted in a comparable suppression of cancer cell migration and EMT. Additionally, JDF treatment inhibited activation of the PI3K/AKT pathway, thus promoting the apoptosis of M2 macrophages. ConclusionsTreatment with JDF reduced the EMT and migratory capacity of liver cancer cells, which might be attributed to the inhibition of M2 macrophage infiltration and interruption of the CSF-1/PI3K/AKT signaling pathway. This mechanism may hold significant implications for mitigating the risk of metastatic spread in the aftermath of hepatic surgery.

Based on machine learning, CDC20 has been identified as a biomarker for postoperative recurrence and progression in stage I & II lung adenocarcinoma patients.

By utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets. To begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment. First, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway. CDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.

Proteomic Analysis of Caco-2 Cells Disrupted by EcN 1917-Derived OMVs Reveals Molecular Information on Bacteria-Mediated Cancer Cell Migration.

Escherichia coli Nissle 1917 (EcN 1917) exhibits distinct tumor-targeting activity, and early studies demonstrated that outer membrane vesicles (OMVs) mediate bacteria-host interactions. To decipher the molecular mechanism underlying the interaction between EcN 1917 and host cells via OMV-mediated communication, we investigated the phenotypic changes in Caco-2 cells perturbed by EcN 1917-derived OMVs and constructed proteomic maps of the EcN 1917-derived OMV components and OMV-perturbed host cells. Our findings revealed that the size of the EcN 1917-derived OMV proteome increased 4-fold. Treatment with EcN 1917-derived OMVs altered the proteomic and phosphoproteomic profiles of host cells. Importantly, for the first time, we found that treatment with EcN 1917-derived OMVs inhibited cancer cell migration by suppressing the expression of ANXA9. In addition, phosphoproteomic data suggested that the ErbB pathway may be involved in OMV-mediated cell migration. Taken together, our study provides valuable data for further investigations of OMV-mediated bacteria-host interactions and offers great insights into the underlying mechanism of probiotic-assisted colorectal cancer therapy.

Disintegrin Accutin inhibits A549 cell migration though suppression of EMT and FAK/AKT signaling pathway

Integrins are heterodimers composed of two subunits, α(120-185kD) and β (90-110kD), which mediate the connection between cells and their external environment, such as extracellular matrix (ECM), and play an important role in the regulation of cell shape, proliferation and migration. Herein, we identified a potent anti-tumor migration peptide Accutin from crude venom of Agkistrodon acutus using an A549 3D tumor sphere model, and simulation tools and RNA sequencing were performed to reveal the mechanism of Accutin. Accutin is a disintegrin and docking, molecular dynamics simulations and ITC assay indicate that the RGD motif in the Accutin sequence can stably bind to integrins α5β1. 9.22 nM Accutin can significantly inhibit the migration and invasion of lung cancer cell lines. Transcriptome analysis indicated that many genes are involved in tumor cell adhesion-related biological processes. Several pathways, like the “mTOR signaling pathway”, “TGF-β signaling pathway”, and “Focal adhesion” were enriched. Interestingly, pathways involved in “N-Glycan biosynthesis” etc. were significantly inhibited. These transcriptomics data suggested that the molecular basis of Accutin-mediated inhibition of cancer cell migration may be by inhibiting N-glycosylation of integrin, then inhibiting signaling pathways such as PI3K/AKT/mTOR and TGFβ/smad. Western blotting analysis further confirmed that Accutin could suppress migration via down-regulating the phosphorylation of FAK and AKT and inhibiting EMT (epithelial-mesenchymal transition). Taken together, as a disintegrin with high efficiency, Accutin may be a potential precursor of a therapeutic agent for the treatment of lung cancer migration.

Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands

Ir(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β-carboline N^N′ ligands have been synthesized, aiming to evaluate the impact of the different metal fragments ([Ir(C^N)2]+ or [Ru(N^N)2]2+) and N^N’ ligands on the photophysical and biological properties. All the compounds exhibit remarkable photostability under blue-light irradiation and are emissive (605 < λem < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pKa values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pKa > 9.3). The presence of the deprotonated form in the Ir-PSs favours the generation of reactive oxygen species (ROS) since, according to theoretical calculations, it features a low-lying ligand-centered triplet excited state (T1 = 3LC) with a long lifetime. All compounds have demonstrated anticancer activity. Ir(III) complexes 1–3 exhibit the highest cytotoxicity in dark conditions, comparable to cisplatin. Their activity is notably enhanced by blue-light irradiation, resulting in nanomolar IC50 values and phototoxicity indexes (PIs) between 70 and 201 in different cancer cell lines. The Ir(III) PSs are also activated by green (with PI between 16 and 19.2) and red light in the case of complex 3 (PI = 8.5). Their antitumor efficacy is confirmed by clonogenic assays and using spheroid models. The Ir(III) complexes rapidly enter cells, accumulating in mitochondria and lysosomes. Upon photoactivation, they generate ROS, leading to mitochondrial dysfunction and lysosomal damage and ultimately cell apoptosis. Additionally, they inhibit cancer cell migration, a crucial step in metastasis. In contrast, Ru(II) complex 6 exhibits moderate mitochondrial activity. Overall, Ir(III) complexes 1–3 show potential for selective light-controlled cancer treatment, providing an alternative mechanism to chemotherapy and the ability to inhibit lethal cancer cell dissemination.

Hyaluronidase inhibitor delphinidin inhibits cancer metastasis

Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular mass hyaluronic acid, a major non-protein component of extracellular matrix, protects naked mole rats from cancer and reduces cancer incidence in mice. Hyaluronidase plays a critical role in degrading hyaluronic acid and is frequently overexpressed in metastatic cancer. Here we investigated the potential of targeting hyaluronidases to reduce metastasis. A high throughput screen identified delphinidin, a natural plant compound found in fruits and vegetables, as a potent hyaluronidase inhibitor. Delphinidin-mediated inhibition of hyaluronidase activity led to an increase in high molecular weight hyaluronic acid in cell culture and in mouse tissues, and reduced migration and invasion behavior of breast, prostate, and melanoma cancer cells. Moreover, delphinidin treatment suppressed melanoma metastasis in mice. Our study provides a proof of principle that inhibition of hyaluronidase activity suppresses cancer cell migration, invasion and metastasis. Furthermore, we identified a natural compound delphinidin as a potential anticancer therapeutic. Thus, we have identified a path for clinical translation of the cancer resistance mechanism identified in the naked mole rat.

Synergic effects and possible mechanism of emodin and stilbene glycosides on colorectal cancer

BackgroundPolygonum multiflorum (PM) is a core herb that enhances immunity. It can also detoxify, reduce swelling, and intercept malaria. Its main components, emodin (EMD) and 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (stilbene glycoside, TSG), have good anti-cancer potential. PurposeThe study aims to investigate synergic effects of EMD and TSG on CRC and its possible mechanism. MethodsNetwork pharmacology and bioinformatics were used to identify targets. HPLC was used to analyze the effective ingredients in PM and to determine the content of the main ingredients. HT-29 cells were used for in vitro experiments. Cell Counting Kit-8 (CCK8) and scratch test were used to detect the effects of various chemical components of PM on the proliferation and migration of HT-29 cells, and Western Bolt (WB) test was used to evaluate the effects of EMD and TSG on P53 pathway. In vivo experiments, the effects of EMD and TSG were evaluated by measuring tumor weight and tumor volume in CRC mice model and histological analysis were carried out with HE staining. The expressions of HSP90, P53, COX2, and ROS were detected by quantitative reverse transcription polymerase chain reaction (PCR), and IL-1β, IL-4, IL-6, IL-10, TGF-β and IFN-γ were detected by enzyme linked immunosorbent assay (ELISA). WB and Immunohistochemistry (IHC) were used to detect the expression of P53 related proteins. ResultsNetwork pharmacology showed PM closely related to colorectal cancer pathway and the core targets included STAT3 and P53; bioinformatics indicated P53 played an important role in the development and prognosis of CRC; chemical analysis showed identified and quantified gallic acid (GA), cis-TSG, trans-TSG, Emodin glucoside(EMDG), physcion glucoside (PHYG), EMD in PM; EMD induced apoptosis and TSG inhibited migration of HT-29 cells; EMD and TSG could coordinately shrink tumor size of CRC mice, elevate expressions of F4/80, decrease the content of IL-6 and TGF-β, promote tumor oxidized and reduce expression of P53 and STAT3 in the tumor. ConclusionsIn vitro experiments showed that TSG inhibited cancer cell migration and EMD induced apoptosis. EMD and TSG had synergic effects on CRC, whose possible mechanism might be to regulate the expression of cytokines and inhibit P53 pathway.

Anticancer potential of silver nanoparticles biosynthesized using Catharanthus roseus leaves extract on cervical (HeLa229) cancer cell line

Cervical cancer is a significant global health issue among women due to its prevalence and impact on morbidity and mortality, especially in low- and middle-income countries. This underscores the critical necessity for the development of anticancer treatments that are not only more efficient but also safer. This study introduces a novel approach to combating cervical cancer by synthesizing silver nanoparticles (AgNPs) using aqueous Catharanthus roseus leaves extract and evaluating their anticancer activity. The aqueous extract of C. roseus showed remarkable potential to reduce silver ions rapidly. UV–Vis spectroscopy confirmed the formation of AgNPs, with a characteristic surface plasmon resonance (SPR) band observed at 429 nm. TEM/EDX and FE-SEM analysis confirmed the presence of spherical AgNPs with uniform size distribution. XRD analysis confirmed the face-centered cubic (FCC) structure of metallic silver in AgNPs. Moreover, AgNPs exhibited significant antiproliferative and cytotoxic effects on HeLa229 cells, with higher selectivity towards cancer cells compared to normal cells. Moreover, wound healing assays showed the robust antimetastatic potential of AgNPs by inhibiting cancer cell migration. The real-time reverse transcription polymerase chain reaction analysis demonstrated the impact of AgNPs on inducing apoptosis and cell cycle arrest. Overall, these findings highlight the promising role of Ag-NPs synthesized from C. roseus extract as effective anticancer agents,offering a promising alternative to conventional chemotherapy with potentially reduced side effects and increased efficacy.

Synthesis, structure, and mechanism of action of a unique mixed-ligand nickel (II)-complex of tetra-dentate phenol-based ligand with di-aquo co-ligands with significant pro-apoptotic and anti-metastatic effect against malignant human cancer cells

From the discovery of the anticancer activity of “cisplatin”, various type of numerous mononuclear platinum (II) complexes has been evaluated for antitumor activities, though therapeutic use is limited due to side effects and resistance. In this study, A unique mixed ligand mono nuclear octahedral Ni (II) complex [NiL(H2O)2].0·.5H2O (1) [H2L = N,Nʹ-dimethyl-N,Nʹ-bis (2-hydroxy-3,5-di methyl benzyl)-ethylenediamine] with tetra dentate phenol based ligand with N2O2 donor environment along with two labile water molecules was synthesised. The complex (1) is structurally characterized by spectroscopic tools including single-crystal X-ray diffractometer. Complex (1) crystallizes in monoclinic space group P21/n with a = 10.4871(17) Å, b = 20.860 (4) Å and c = 20.955(4) Å. The UV – visible spectra show two peaks around 507 nm and 367 nm due to spin-allowed 1A1g → 1A2g and 1A1g → 1B1g transitions respectively as expected for a square planar d8 system. Mixed ligand octahedral nickel (II) complex with facially coordinating tetra dentate phenol-based ligand (H2L) is in association with two water molecule as ancillary ligand. Two water molecules associated with coordination zone of nickel (II) centre is loosely bound. In this present study, we have evaluated the anti-cancer properties of Complex (1). We found that Complex (1) show potent cancer cell killing activity in case of poorly invasive mice and human cancer cell lines. Complex (1) trigger apoptosis chiefly via p53 dependent pathway. Complex (1) also inhibits cancer cell migration and epithelial to mesenchymal transition in case of metastatic breast cancer cells suggesting potent anti-cancer properties of complex (1).

F10 Gene Expression and Ethnic Disparities Present in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by the F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data were acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p < 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed, corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high-expression cohort, correlating with the lower disease-free rates observed in the Hispanic patient cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

Identification of a novel prognostic cuproptosis-associated LncRNA signature for predicting prognosis and immunotherapy response in patients with esophageal cancer

Nowadays, effective prognostic models for esophageal cancer (ESCA) are still lacking. Long noncoding RNAs (lncRNAs) are commonly utilized as indicators for diagnosing cancer and forecasting patient outcomes. Cuproptosis is regulated by multiple genes and is crucial to the progression of ESCA. However, it is not yet clear what role the cuproptosis-associated lncRNAs (CuALs) play in ESCA. To tackle this problem, a prognostic signature incorporating three CuALs was created. This signature was constructed by the use of the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. Subsequently, the signature effectively stratified ESCA samples into a high-risk group and a low-risk group. Those in the low-risk group demonstrated extended overall survival (OS), as well as increased infiltration of T cells, macrophages, and NK cells, suggesting a potentially enhanced response to immunotherapy. The ROC curve analysis demonstrated that this prognostic signature outperformed conventional clinical factors in predicting patient prognosis (AUC = 0.708). K-M survival analysis and correlation analysis identified UGDH-AS1 (a CuAL) as a protective factor positively associated with patient prognosis. The results of RT-qPCR and wound healing assays indicated that UGDH-AS1 is overexpressed in ESCA and could inhibit cancer cell migration. In general, the prognostic signature of CuALs demonstrated a robust capability in forecasting the immune environment and patient prognosis, highlighting its potential as a tool for enhancing personalized treatment strategies in ESCA.