Inhibited Tumor Cell Proliferation Research Articles

In situ enzymatic peptide-based nanomedicine with combined effects for enhanced tumor radio-immunotherapy

Despite the combination of radiotherapy and immunotherapy in clinical practice have shown promising synergistic anti-tumor effect, the immunosuppressive tumor microenvironment (TME) remains to be one of stumbling block impeding the therapeutic efficacy of radio-immunotherapy. In this study, in situ self-assembled peptide-based drug delivery systems with multiple effects were constructed for enhancing tumor radio-immunotherapy. The two peptide-drug conjugates could co-assembled into peptide-based nanomedicine on the cancer cell membrane under enzyme catalysis and continuously release small molecular active drugs in the cytoplasm, which combined action lead YAP phosphorylation and nuclear transfer failure. By simutaneously suppressing glycolysis and reactivating the dysfunctional Hippo pathway, the peptide-based nanomedicine also remitted the immunosuppressive TME by reducing lactate levels and the expression of immunosuppressive factors, respectively. As a result, the pro-tumorigenic M2 phenotype of tumor-associated macrophages (TAMs) was decreased and the anti-tumorigenic M1 phenotype of TAMs was increased. Such a dual intervention strategy from cellular metabolic level and gene transcription level not only inhibited tumor cell proliferation but also reversed the immunosuppressive TME, thereby augmenting the combined efficacy of radiotherapy and immune checkpoint blockade (ICB) therapy. The work is anticipated to contribute novel insights into anti-cancer drug targeted delivery and tumor multi-modal synergistic therapy.

Non-canonical RNA-binding protein ANXA11 regulates microRNA resorting into small extracellular vesicles to mediate cisplatin resistance.

The sensitivity of laryngeal squamous cell carcinoma (LSCC) to chemotherapy shows large heterogeneity. The role of miRNA in small extracellular vesicles (sEV) in chemotherapy resistance is under investigation. However, the regulation and sorting mechanism of sEV miRNAs remains unclear. In this study, small RNA sequencing was used to explore miRNA expression profiles in sEV of LSCC after cisplatin stimulation; RNA pull-down, mass spectrometry, and EMSA were used to clarify the binding of candidate RNA-binding protein (RBP) and candidate miRNA. Immunostaining and microRNA fluorescence insitu hybridization were performed to identify how candidate RBP affects miRNA stability and nuclear/cytoplasmic distribution. Invivo experiments were performed to verify the biological functions and response to cisplatin of candidate RBP. We found that cisplatin stimulation induced increased expression of miR-148a-3p and sEV sorting. ANXA11 binds to miR-148a-3p in a sequence-specific manner. ANXA11 inhibits tumor cell proliferation and drug resistance by binding to and retaining miR-148a-3p. Cisplatin stimulation reduced ANXA11 expression and promoted miR-148a-3p efflux through sEV pathways. ANXA11 overexpression reduced invivo tumor proliferation and cisplatin-resistance. Taken together, ANXA11 mediates cisplatin resistance through sEV miRNA resorting. Mechanically, ANXA11 binds to miR-148a-3p in a sequence-specific manner to regulate its resorting and thus influences tumor proliferation and chemoresistance.

Taohong Siwu decoction enhances the chemotherapeutic efficacy of doxorubicin by promoting tumor vascular normalization

BackgroundInstead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of “blood-activating and stasis-resolving” formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. PurposeTo study the underlying mechanisms of a classical “blood-activating and stasis-resolving” formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. Study designHUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. ResultsOur data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206+ macrophages and increased number of CD86+ macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. ConclusionThis study demonstrated for the first time that TSD as a classical Chinese formula can enhance the drug efficacy and reduce the side effects of doxorubicin. These findings can support that TSD could be used as an adjuvant therapy in combination with conventional chemotherapy for the future breast cancer treatment.

Design, synthesis, and evaluation of antitumor activity in Pseudolaric acid B Azole derivatives: Novel and potent angiogenesis inhibitor via regulation of the PI3K/AKT and MAPK mediated HIF-1/VEGF signaling pathway

Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized and assessed for their capacity to suppress VEGF secretion in SiHa cells under hypoxic conditions. Notably, majority of these derivatives exhibited significant inhibition of VEGF protein secretion without inducing cytotoxicity. Among them, compound M2 displayed the most potent inhibitory activity, with an IC50 value of 0.68 μM, outperforming the lead compound PAB (IC50 = 5.44 μM). Compound M2 not only curbed the migration and angiogenesis of HUVECs under hypoxic conditions but also hindered the invasion of SiHa cells. Mechanistic investigations unveiled that compound M2 may impede the accumulation and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) in SiHa cells, thereby downregulating VEGF expression. This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis. Furthermore, compound M2 was observed to modulate the PI3K/AKT/mTOR and MAPK signaling pathways in tumor cells, thereby regulating HIF-1α translation and synthesis. In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.

Extracellular vesicles derived from mesenchymal stem cells suppress breast cancer progression by inhibiting angiogenesis.

Previous studies have highlighted the antitumor effects of mesenchymal stem cell‑derived extracellular vesicles (MSC‑EVs), positioning them as a promising therapeutic avenue for cancer treatment. However, some researchers have proposed a bidirectional influence of MSC‑EVs on tumors, determined by the specific tissue origin of the MSCs and the types of tumors involved. The present study aimed to elucidate the effects of human placenta MSC‑derived extracellular vesicles (hPMSC‑EVs) on the malignant behavior of a mouse breast cancer model of 4T1 cells in vitro and in vivo. The findings revealed that hPMSC‑EVs significantly inhibited the proliferation, migration and colony formation of cultured 4T1 mouse breast cancer cells without inducing apoptosis. Exposure to conditioned medium from 4T1 cells pretreated with hPMSC‑EVs resulted in decreased angiogenic activity, accompanied by the downregulation of angiogenesis‑promoting genes in human umbilical vein endothelial cells. In murine xenograft models derived from the 4T1 cell line, local administration of hPMSC‑EVs substantially hindered tumor growth. Further results revealed that hPMSC‑EVs inhibited angiogenesis in vivo, as reflected by the use of a vascular growth factor receptor 2‑Fluc transgenic mouse model. In summary, the results confirmed that hPMSC‑EVs negatively modulated breast cancer growth by suppressing tumor cell proliferation and migration via an indirect antiangiogenic mechanism. These results underscored the therapeutic potential of EVs, suggesting a promising avenue for alternative anticancer treatments in the future.

Triterpenes from Ganoderma lucidum inhibit hepatocellular carcinoma by regulating enhancer-associated lncRNA in vivo

Ethnopharmacological relevanceGanoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment. Aim of the studyTo explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments. Materials and methodsHepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene. ResultsKi67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells. ConclusionsEnhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.

Progress, pharmacokinetics and future perspectives of luteolin modulating signaling pathways to exert anticancer effects: A review.

Luteolin (3, 4, 5, 7-tetrahydroxyflavone) are natural flavonoids widely found in vegetables, fruits and herbs, with anti-tumor, anti-inflammatory and antioxidant effects, and also play an anti-cancer effect in various cancers such as lung, breast, prostate, and liver cancer, etc. Specifically, the anti-cancer mechanism includes regulation of various signaling pathways to induce apoptosis of tumor cells, inhibition of tumor cell proliferation and metastasis, anti-angiogenesis, regulation of immune function, synergistic anti-cancer drugs and regulation of reactive oxygen species levels of tumor cells. Specific anti-cancer mechanisms include regulation of various signaling pathways to induce apoptosis, inhibition of tumor cell proliferation and metastasis, anti-angiogenesis, reversal of epithelial-mesenchymal transition, regulation of immune function, synergism with anti-cancer drugs and regulation of reactive oxygen species levels in tumor cells. This paper integrates the latest cutting-edge research on luteolin and combines it with the prospect of future clinical applications, aiming to explore the mechanism of luteolin exerting different anticancer effects through the regulation of different signaling pathways, so as to provide a practical theoretical basis for the use of luteolin in clinical treatment and hopefully provide some reference for the future research direction of luteolin.

The Ubiquitin E3 Ligase FBXO33 Suppresses Stem Cell-Like Properties and Metastasis in Non-Small-Cell Lung Cancer by Promoting Ubiquitination and Degradation of Myc.

Non-small cell lung cancer (NSCLC) is a malignant form of lung cancer, and its prognosis could be improved by identifying key therapeutic targets. Thus, this study investigates the potential role of F-box Only Protein 33 (FBXO33) in NSCLC. The expression levels of FBXO33 in NSCLC were determined using University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) prediction, and its correlation with overall survival (OS) was analyzed via Kaplan-Meier survival analysis. These results were validated through quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence (IF). We modulated FBXO33 expression by overexpression or knockdown and analyzed its effects on cell growth, proliferation, migration, invasion, and stemness characteristics in NSCLC cell lines. Additionally, the interaction between FBXO33 and Myelocytomatosis (Myc) and its impact on Myc ubiquitination were examined. An in vivo NSCLC xenograft model was used to corroborate the in vivo experimental results. The study found an inverse correlation between FBXO33 expression in NSCLC and OS. Lower FBXO33 expression enhanced the growth, proliferation, migration, invasion, and stemness characteristics of NSCLC cell lines. FBXO33 interacted with Myc to promote its ubiquitination and subsequent degradation, which suppressed NSCLC development. FBXO33 is expressed at low levels in NSCLC and correlates with lower OS. Overexpression of FBXO33 promotes Myc ubiquitination and degradation and inhibits tumor cell proliferation, migration and stemness characteristics, thereby impeding NSCLC progression.

Mechanisms of Yiai Fuzheng formula in the treatment of triple-negative breast cancer based on UPLC-Q-Orbitrap-HRMS, network pharmacology, and experimental validation

Ethnopharmacological relevanceYiai Fuzheng formula (YAFZF), as a Traditional Chinese Medicine (TCM) prescription, has been used widely at Zhongnan Hospital of Wuhan University for its therapeutic effects and high safety on triple-negative breast cancer (TNBC). ObjectiveIn this study, we employed ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS), network pharmacology, and experimental validation to elucidate the underlying action mechanism of YAFZF in the treatment of TNBC. MethodsThe key active ingredients in YAFZF were analyzed using UPLC-Q-Orbitrap-HRMS, and then the potential components, target genes and signalling pathways of YAFZF were predicted using the network pharmacological method. We then used molecular docking to visualize the combination characteristics between major active components and macromolecules in the crucial pathway. In vitro experiments were conducted to investigate the inhibitory effects of YAFZF treatment on the cell viability, invasion, and migration of 4T1 and MDA-MB-231 cells. The xenograft TNBC models were constructed using female Balb/c mice, and their body weights, tumour volumes, and weights were monitored during YAFZF treatment. Quantitative real-time PCR (qRT-PCR), Hematoxylin-eosin (HE), immunohistochemistry (IHC) staining, Western blot (WB), and terminal deoxynucleotidyl transferase (TdT)-dUTP nick-end labeling (TUNEL) staining were used for further experimental validation. ResultsBased on UPLC-Q-Orbitrap-HRMS and network pharmacology analysis, 6 major bioactive components and 153 intersecting genes were obtained for YAFZF against TNBC. Functional enrichment analysis identified that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway might be the mechanism of action of YAFZF in the treatment of TNBC. Molecular docking results suggested that the main active compounds in YAFZF had strong binding energies with the proteins in the PI3K/Akt pathway. In vitro experiments showed that YAFZF inhibited the cell viability, invasion, and migration abilities of TNBC cells. Animal experiments confirmed that YAFZF treatment suppressed tumour cell proliferation and increased apoptotic cells. PCR, HE, WB, and IHC results indicated that YAFZF could suppress xenograft tumour metastases by inhibiting the PI3K/AKT/mTOR pathway regulating the epithelial-mesenchymal transition (EMT) process. ConclusionYAFZF therapy showed its potential for reducing proliferation, invasion, and migration abilities, increasing apoptosis of TNBC cells. Furthermore, YAFZF treated TNBC by inhibiting xenograft tumour distant metastases via the regulation of EMT by the PI3K/Akt/mTOR pathway, suggesting that it may be useful as an adjuvant treatment.

Optimizing ABA-based chemically induced proximity for enhanced intracellular transcriptional activation and modification response to ABA.

Abscisic acid (ABA)-based chemically induced proximity (CIP) is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1 (PYL1) and the 2C-type protein phosphatase ABI1, which confers ABA-induced proximity to their fusion proteins, and offers precise temporal control of a wide array of biological processes. However, broad application of ABA-based CIP has been limited by ABA response intensity. In this study, we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1 (PYR1) and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells. We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells. We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13, successfully inhibiting tumor cell proliferation. We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution (PACE), successfully generating a PYR1 mutant (PYR1m) whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type. In addition, we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type. These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE, providing a new approach for the modification of other CIP systems.

Enhancement of the anticancer potential and biosafety of BSA-modified, bacterial membrane-coated curcumin nanoparticles

Bacteria and bacterial components have been widely used as bionanocarriers to deliver drugs to treat tumors. In this study, we isolated bacterial outer membrane vesicles (OMVs) with good stability and high yield for macrophage polarization and cell recruitment. Using ultrasound baths, these bacterial OMVs were combined with curcumin nanoparticles (OMV CUR NPs), following which these nanoparticles were modified with bovine serum albumin (BSA) to achieve high biosafety and tumor-targeting effects. The particle size, PDI, and zeta potential of the BSA-OMV CUR NPs were 157.9 nm, 0.233, and −15.1 mV, respectively. The BSA-OMV CUR NPs exhibited high storage stability, low cytotoxicity, sustained release, enhanced cellular uptake of CUR, induction of tumor cell apoptosis, and inhibition of tumor cell proliferation and migration. By determining the survival rate, body length, heart rate, head size, eye size, and pericardium size of the zebrafish, we found that the BSA-OMV CUR NPs were safe for application in vivo. Moreover, an increase in antiproliferation, antiangiogenic and antimetastatic effects of BSA-OMV CUR NPs was demonstrated in wild-type and transgenic tumor-transplanted zebrafish embryos.

Fe-doped 45S5 bioactive glass compositions impair the metabolic activity and proliferation of metastatic human breast cancer cells in vitro

Many kinds of human tumors, including breast carcinomas, frequently metastasize to the bone, making it prone to pathologic fractures. Surgical management of bone metastases ranges from the resection of metastases to bone repair. Current surgical methods for the repair of bone defects include the use of polymethyl methacrylate (PMMA)-based bone cements. A promising alternative material are bioactive glass (BG) particles that in addition to providing physical stability can also induce bone regeneration. Moreover, BGs doped with Fe2O3may also have a negative impact on tumor cells. Here, we tested the hypothesis that BGs can affect metastatic human breast cancer cells. To this end, we assessed the effects of different BG compositions with and without Fe2O3on metastatic human MDA-MB-231 breast cancer cellsin vitro. We found that all BGs tested impaired the viability and proliferation of breast cancer cells in a concentration-dependent manner. The anti-proliferative effects inversely correlated with BG particle size, and were in general less pronounced in mesenchymal stromal cells (MSCs) that served as a control. Moreover, Fe2O3-doped BGs were more potent inhibitors of tumor cell proliferation and metabolic activity than Fe2O3-free BG. Our data therefore indicate that BGs can affect human breast cancer cells more strongly than MSCs, and suggest that the presence of Fe2O3can potentiate anti-proliferative and anti-metabolic effects of BGs. Fe2O3-doped BGs thus have the potential to be used for the surgical management of metastatic bone lesions, and may in addition to their regenerative properties also allow the local control of bone metastases.

Avapritinib efficacy in primary hepatic neuroendocrine carcinoma with elevated PDGFRA expression: Insights from a PDX model study

Background & aimsPrimary Hepatic Neuroendocrine Carcinoma (PHNEC) is a rare and aggressive tumor with high recurrence rates. Surgical resection remains the only therapeutic strategy. The effectiveness of tyrosine kinase inhibitors (TKIs) for PHNEC remains unclear due to limited research. MethodsWe employed immunohistochemical staining to diagnose PHNEC and assess the expression of eight tyrosine kinase receptors in tumor tissues, including VEGFRs, PDGFRA, EGFR, FGFRs et al. A patient-derived xenograft (PDX) model was established using PHNEC tumor tissues to test the efficacy of TKIs. PDX mice bearing tumors were treated with Avapritinib, an FDA-approved PDGFRA-targeting drug, at a daily oral dose of 10 mg/kg for 2 weeks. ResultsPathological analysis confirmed the diagnosis of PHNEC with positive expression of Neural cell adhesion molecule (NCAM/CD56), Synaptophysin (Syn), and Somatostatin receptor 2 (SSTR-2), and negative expression of Hep (Hepatocyte Paraffin 1), a biomarker for Hepatocellular carcinoma. Notably, PDGFRA was significantly overexpressed in PHNEC tumor tissues compared to other tyrosine kinases. Avapritinib treatment significantly reduced tumor growth in PDX mice by 73.9 % (p = 0.008). Additionally, Avapritinib treatment led to a marked decrease in PDGFRA and Ki-67 expression, suggesting that it inhibits tumor cell proliferation by suppressing PDGFRA. ConclusionOur findings suggest that PDGFRA is a potential therapeutic target for PHNEC, and its inhibition with Avapritinib may offer clinical benefits to patients with this rare malignancy.

Growth inhibition of pancreatic cancer by targeted delivery of gemcitabine via fucoidan-coated pH-sensitive liposomes

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of −19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.

Anti-tumor effect and hepatotoxicity mechanisms of psoralen.

In recent years, natural products have gradually become an important source for new drug development due to their advantages of multi-components, multi-targets, and good safety profiles. Psoralen, a furanocoumarin compound extracted from the traditional Chinese medicine psoralea corylifolia, is widely distributed among various plants. It has attracted widespread attention in the research community due to its pharmacological activities, including antitumor, anti-inflammatory, antioxidant, and neuroprotective effects. Studies have shown that psoralen has broad spectrum anti-tumor activities, offering resistance to malignant tumors such as breast cancer, liver cancer, glioma, and osteosarcoma, making it a natural, novel potential antitumor drug. Psoralen mainly exerts its antitumor effects by inhibiting tumor cell proliferation, inducing apoptosis, inhibiting tumor cell migration, and reversing multidrug resistance, presenting a wide application prospect in the field of antitumor therapy. With the deepening research on psoralea corylifolia, its safety has attracted attention, and reports on the hepatotoxicity of psoralen have gradually increased. Therefore, this article reviews recent studies on the mechanism of antitumor effects of psoralen and focuses on the molecular mechanisms of its hepatotoxicity, providing insights for the clinical development of low-toxicity, high-efficiency antitumor drugs and the safety of clinical medication.

Cytotoxicity assessment of Cu0.5Zn0.5Fe2O4 nanoparticles prepared via rapid combustion-calcination process on SGC-7901 and HGC-27 gastric cancer cells

Currently, ferrite magnetic nanoparticles are widely utilized in the biomedical domain, encompassing antibacterial, catalytic, imaging, and drug delivery among other fields. In this study, Cu0.5Zn0.5Fe2O4 nanoparticles were synthesized via the rapid combustion-calcination process. By incorporating inorganic metal elements with specific functionalities, the limitations of iron oxide could be overcome, enabling targeted roles in various applications. The morphology, phase composition, and magnetic properties were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). The impact of anhydrous ethanol quantity, calcination temperature, and duration on the magnetic properties and grain size of the nanomaterials was investigated. Cu0.5Zn0.5Fe2O4 nanoparticles were evaluated for their inhibitory effects on human gastric cancer cells (SGC-7901 and HGC-27) under different preparation conditions. The results of the MTT assay revealed a concentration - and time-dependent inhibition of tumor cell proliferation by Cu0.5Zn0.5Fe2O4 nanoparticles. Nanoparticles exhibiting a magnetic energy of 20.23 emu/g and an average particle size of 51.6 nm, synthesized using 20 mL of anhydrous ethanol, calcination temperature of 400 °C, and a calcination duration of 2.0 h, displayed significant inhibitory effects on tumor cells. Furthermore, The nanoparticles not only showed low toxicity to human normal stomach cells GES-1, but also enhanced the inhibitory effect on tumor cells under the action of an external magnetic field.

A platelet-related signature for predicting the prognosis and immunotherapy benefit in bladder cancer based on machine learning combinations.

Bladder cancer carries a large societal burden, with over 570,000 newly diagnosed cases and 210,000 deaths globally each year. Platelets play vital functions in tumor progression and therapy benefits. We aimed to construct a platelet-related signature (PRS) for the clinical outcome of bladder cancer cases. Ten machine learning techniques were used in the integrative operations to build PRS using the datasets from The Cancer Genome Atlas (TCGA), gene series expression (GSE)13507, GSE31684, GSE32894 and GSE48276. A number of immunotherapy datasets and prediction scores, including GSE91061, GSE78220, and IMvigor210, were utilized to assess how well the PRS predicted the benefit of immunotherapy. Vitro experiment was performed to verify the role of α1C-tubulin (TUBA1C) in bladder cancer. Enet (alpha =0.4) algorithm-based PRS had the highest average C-index of 0.73 and it was suggested as the optimal PRS. PRS acted as an independent risk factor for bladder cancer and patients with high PRS score portended a worse overall survival rate, with the area under the curve of 1-, 3- and 5-year operating characteristic curve being 0.754, 0.779 and 0.806 in TCGA dataset. A higher level of immune-activated cells, cytolytic function and T cell co-stimulation was found in the low PRS score group. Low PRS score demonstrated a higher tumor mutation burden score and programmed cell death protein 1 & cytotoxic T-lymphocyte associated protein 4 immunophenoscore, lower tumor immune dysfunction and exclusion score, intratumor heterogeneity score and immune escape score in bladder cancer, suggesting the PRS as an indicator for predicting immunotherapy benefits. Vitro experiment showed that TUBA1C was upregulated in bladder cancer and knockdown of TUBA1C obviously suppressed tumor cell proliferation. The present study developed an ideal PRS for bladder cancer, which may be used as a predictor of prognosis, a risk classification system, and a therapy guide.

Single-cell transcriptomic sequencing analysis of mechanistic insights into the IFN-γ signaling pathway in different tumor cells.

This study aimed to investigate the relationship between the interferon-gamma (IFN-γ) pathway in different tumor microenvironments (TME) and patients' prognosis, as well as the regulatory mechanisms of this pathway in tumor cells. Using RNA-seq data from the TCGA database, we analyzed the predictive value of the IFN-γ pathway across various tumors. We employed a univariate Cox regression model to assess the prognostic significance of IFN-γ signaling in different tumor types. Additionally, we analyzed single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to examine the distribution characteristics of the IFN-γ pathway and explore its regulatory mechanisms, highlighting how IFN-γ influenced cellular interactions within the TME. Our analysis revealed a significant association between the IFN-γ pathway and adverse prognosis in pan-cancer tissues (P < 0.001). Interestingly, this correlation varied regarding positive and negative regulation across different tumor types. Through a detailed examination of scRNA-seq data, we found that the IFN-γ pathway exerted substantial regulatory effects on stromal and immune cells. In contrast, its expression and regulatory patterns in tumor cells exhibited diversity and heterogeneity. Further analysis indicated that the IFN-γ pathway not only enhanced the immunogenicity of tumor cells but also inhibited their proliferation. Cell-cell interaction analysis confirmed the pivotal role of the IFN-γ pathway within the overall regulatory network. Moreover, we identified HMGB2 (high mobility group box 2) in T cells as a potential key regulator of tumor cell proliferation. The IFN-γ pathway exhibited a dual function by both suppressing tumor cell proliferation and enhancing their immunogenicity, positioning it as a pivotal target for refined cancer diagnosis and cancer strategies.

Advances in the anti-tumor mechanisms of saikosaponin D.

Saikosaponin D, a saponin compound, is extracted from Bupleurum and is a principal active component of the plant. It boasts a variety of pharmacologic effects including anti-inflammatory, antioxidant, immunomodulatory, metabolic, and anti-tumor properties, drawing significant attention in anti-tumor research in recent years. Research indicates that saikosaponin D inhibits the proliferation of numerous tumor cells, curbing the progression of cancers such as liver, pancreatic, lung, glioma, ovarian, thyroid, stomach, and breast cancer. Its anti-tumor mechanisms largely involve inhibiting tumor cell proliferation, promoting tumor cell apoptosis, thwarting tumor-cell invasion, and modulating tumor cell autophagy. Moreover, saikosaponin D enhances the sensitivity to anti-tumor drugs and augments body immunity. Given its multi-faceted anti-tumor roles, saikosaponin D offers promising potential in anti-tumor therapy. This paper reviews recent studies on its anti-tumor effects, aiming to furnish new theoretical insights for clinical cancer treatments.

Kuwanon C Inhibits Tumor Cell Proliferation and Induces Apoptosis by Targeting Mitochondria and Endoplasmic Reticulum.

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.