Apoptosis In Cancer Cells Research Articles

FATS inhibits the Wnt pathway and induces apoptosis through degradation of MYH9 and enhances sensitivity to paclitaxel in breast cancer.

Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells' migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Unveiling the therapeutic potential of anthocyanin/cisplatin-loaded chitosan nanoparticles against breast and liver cancers

Abstract Background Liver and breast cancers are among the leading causes of cancer-related deaths worldwide, prompting researchers to seek natural anticancer agents and reduce chemotherapy side effects. Red beetroot (Beta vulgaris Linnaeus), rich in polyphenols and powerful antioxidants, has shown potential in cancer prevention. This study aimed to evaluate the impact of red beetroot-derived anthocyanin (Ant), Ant-loaded chitosan nanoparticles (Ant NPs), cisplatin (Cis), Cis-loaded chitosan (Cis NPs), and Cis + Ant-loaded chitosan NPs on human hepatoma HepG2 and breast adenocarcinoma MCF7 cell lines. Methods NPs preparation was evaluated by zeta potential, FTIR, and SEM. The cytotoxic, apoptotic, antioxidant, anti-inflammatory, anti-metastatic, and anti-angiogenic effects were assessed by MTT assay, qPCR, AO/EB staining, and flow cytometry. Results Treatment with Ant, Ant NPs, Cis, Cis NPs, and Cis + Ant NPs caused cytotoxicity in HepG2 and MCF7 with best effect in Cis-treated cells. The anticancer effects were attributed to mitochondrial-dependent apoptosis (with high Bax and low Bcl2 expression), chromatin disintegration, and cell cycle arrest in G2/M and S phases. All treatments inhibited migration by downregulating the migration-related gene MMP9 and upregulating the anti-migratory gene TIMP1 and decreased the angiogenesis-related gene VEGF and the inflammatory gene TNFα with best results in Cis NPs-treated cells. Interestingly, Ant, Ant NPs, and Cis + Ant NPs increased the antioxidant status (high GSH and upregulated expression of Nrf2 and OH-1) and decreased drug resistance-related MAPK1 and MDR1 genes compared to Cis and Cis NPs-treated cells. Conclusions Anthocyanin and cisplatin-loaded chitosan nanoparticles effectively combat breast and liver cancers by inducing cancer cell apoptosis, enhancing antioxidant defenses, and reducing inflammation. They also inhibit tumor spread and blood vessel formation through downregulation of MMP9 and VEGF, highlighting their therapeutic potential.

The potential of kaempferol in digestive system tumors: recent advances and mechanistic insights.

Digestive system neoplasms are a heterogeneous group of cancers characterized by diverse symptoms, complex diagnosis, and treatment. Prognosis is poor and influenced by multiple factors, making early detection and comprehensive treatment crucial for patient survival. Kaempferol, a flavonoid compound, has attracted attention due to its anti-tumor biological activity, holding promise as a potential drug for treating digestive system neoplasms. Derived from various plants such as cabbage, propolis, and grapefruit, this compound's anti-inflammatory, antioxidant, and other pharmacological effects have been confirmed. Research has found that kaempferol inhibits the occurrence and development of digestive system neoplasms by inducing apoptosis in cancer cells, inhibiting tumor cell proliferation, suppressing tumor metastasis and invasion, and enhancing the effects of other cancer treatment methods. This paper summarizes the role and mechanisms of kaempferol in the study of digestive system neoplasms, providing valuable insights for both scientists and clinical physicians engaged in this field. By detailing the various pathways through which kaempferol exerts its anticancer effects, the paper not only highlights its potential as a therapeutic agent but also opens avenues for further research into its applications.

Anticancer and antiproliferative activities of Algerian Origanum majorana L.’s essential oil on PC-3 and SKBR3 cells

Cancer is a prominent cause of death globally, with breast cancer and prostate cancer being among the most devastating types. Therefore, the available anticancer treatments have some drawbacks, like higher toxicity and limited bioavailability. Thus, this study aimed to investigate for the first time the anticancer activity of Algerian Origanum majorana L.’s essential oil (OMEO). This research assessed the chemical profile of Algerian OMEO by gas chromatography coupled with mass spectrometry (GC-MS). The analysis revealed 29 compounds, which represent 98.08% of total volatile oil. The major compounds identified in OMEO were terpinen-4-ol (21.37%), γ-terpinene (15.78%), α-terpinene (10.43%), and trans-sabinene hydrate (9.27%). Additionally, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) was also used to test the cytotoxicity on prostate cancer (PC-3), breast cancer (SKBR3), and normal retinal pigment epithelium (ARPE-19) cell lines. The results showed a selective cytotoxicity effect by decreasing cell viability of PC-3 cancer cells with half inhibitory concentration (IC50) of 608.57 μg/mL and 672.5 μg/mL after 48h and 72h, respectively. Regarding SKBR3 cancer cells, the IC50 was 991.5 μg/mL. OMEO exhibited no significant cytotoxicity against normal (ARPE-19) cells. Furthermore, we conducted a cell apoptosis assay using Hochest 33342 dye to explore the potential mechanism pathway of OMEO. The findings verified that OMEO could trigger apoptosis in PC-3 and SBKR3 cancer cells. The ability of OMEO to inhibit cell migration assessed via wound healing assay revealed a significant decrease in cell migration. Our results imply that OMEO decreases cell viability by inducing cell apoptosis. Moreover, the oil suppresses cell migration in prostate cancer and breast cancer cells.

MDM2 drives resistance to Osimertinib by contextually disrupting FBW7-mediated destruction of MCL-1 protein in EGFR mutant NSCLC.

Overcoming resistance to Osimertinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is clinically challenging because the underlying mechanisms are not fully understood. The murine double minute 2 (MDM2) has been extensively described as a tumor promotor in various malignancies, mainly through a negative regulatory machinery on the p53 tumor suppressor. However, the significance of MDM2 on the sensitivity to Osimertinib has not been described. Osimertinib resistant cells were generated by standard dose escalation strategy and individual resistant clones were isolated for MDM2 testing. The MDM2 and its mutant constructs (ΔPBD, ΔRING, C464A) were introduced into PC-9, HCC827 and H1975 cells and evaluated for the sensitivity to Osimertinib by MTT assay, colony formation, EdU assay and TUNEL assay. MDM2 expression in resistant cells was manipulated by pharmacological and molecular approaches, respectively. Proteins that were implicated in PI3K/Akt, MAPK/Erk and apoptosis signaling were measured by Western blot analysis. Candidate proteins that interacted with MDM2 were captured by immunoprecipitation and probed with indicated antibodies. In comparison with parental PC-9 cells, the PC-9 OR resistant cells expressed high level of MDM2. Ectopic expression of MDM2 in PC-9, HCC827 and H1975 sensitive cells generated an Osimertinib resistant phenotype, regardless of p53 status. MDM2 promoted resistance to Osimertinib through a PI3K/Akt and MAPK/Erk-independent machinery, in contrast, MDM2 selectively stabilized MCL-1 protein to arrest Osimertinib-induced cancer cell apoptosis. Mechanistically, MDM2 acted as a E3 ligase to ubiquitinate FBW7, a well-established E3 ligase for MCL-1, at Lys412 residue, which resulted in FBW7 destruction and MCL-1 stabilization. Targeting MDM2 to augment MCL-1 protein breakdown overcame resistance to Osimertinib in vitro and in vivo. Finally, the clinical relevance of MDM2-FBW7-MCL-1 regulatory axis was validated in mouse xenograft tumor model and in NSCLC specimen. Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.

Identification of Active Ingredients in Ginseng Volatile Oil: A Strategy Combining Computer Virtual Screening With Experimental Validation.

Ginseng volatile oil (GVO) is a valuable active ingredient in ginseng (Panax ginseng C. A. Mey.) with high research potential. Drying procedures alter the real composition of the fresh material, for example, the evaporation of compounds with low boiling point. In this study, the composition of volatile oil in fresh ginseng (FG), sun-dried ginseng (SDG), and red ginseng (RD) was systematically analyzed to clarify the dominant components of FG and their potential pharmacological effects, which provides a basis for application and development of FG. GVO was obtained through water vapor distillation and analyzed using GC-MS. Pattern recognition analysis was employed to differentiate components in three processed types of ginseng. Based on this analysis, the active ingredients and key targets were screened. The binding mode and affinity were verified using molecular docking technology. Finally, the anticancer activity of GVO was verified by cell experiments. A total of 53 components were identified in three processed types of ginseng by GC-MS. Among them, 32 differential components were screened by pattern recognition analysis. Ultimately, 6 active ingredients (panaxydol, nerolidyl acetate, falcarinol, cis-β-farnesene, γ-elemene, and β-elemene) and 15 key targets were determined by network pharmacology analysis. Molecular docking results revealed that β-elemene exhibited a higher affinity with EGFR, ESR1, and ERK2. Cell experiments indicated that GVO promotes apoptosis in cancer cells. This research proposed a strategy that integrated "component detection-virtual multitarget screening-active component prediction-experimental verification" to expedite the identification of active ingredients, providing insights for application of FG and the development of functional products.

SITP: A single cell bioinformatics analysis flow captures proteasome markers in the development of breast cancer.

Single cell sequencing and related databases have been widely used in the exploration of cancer occurrence and development, but there is still no in-depth explanation of specific and complicated cellular protein modification processes. Ubiquitin-Proteasome System (UPS), as a specific and precise protein modification and degradation process, plays an important role in the biological functions of cancer cell proliferation and apoptosis. Proteasomes, vital multi-catalytic proteinases in eukaryotic cells, play a crucial role in protein degradation and contribute to tumor regulation. The 26S proteasome, part of the ubiquitin-proteasome system. In this study, we have enrolled a common SITP process including analysis of single cell sequencing to elucidate a flow that can capture typical proteasome markers in the oncogenesis and progression of breast cancer. PSMD11, a key component of the 26S proteasome regulatory particle, has been identified as a critical survival factor in cancer cells. Results suggest that PSMD11's rapid degradation is linked to acute apoptosis in cancer cells, making it a potential target for cancer treatment. Our study explored the potential mechanisms of PSMD11 in breast cancer development. The findings revealed the feasibility of disclosing ubiquitinating biomarkers from public database, as well as presented new evidence supporting PSMD11 as a potential therapeutic biomarker for breast cancer.

Tripartite motif-containing protein 50 suppresses triple-negative breast cancer progression by regulating the epithelial–mesenchymal transition

ABSTRACT Background and Objectives Tripartite motif-containing protein 50 (TRIM50) is a recently discovered E3 ubiquitin ligase that participates in tumor progression. TRIM50 is overexpressed in many cancers, although few studies focused on TRIM50‘s role in breast cancer. Methods We overexpressed TRIM50 in triple-negative breast cancer cell lines using plasmid and found that TRIM50 upregulation markedly reduced breast cancer cell proliferation, clone formation, and migration, as well as promoted breast cancer cell apoptosis. Western blotting revealed that accumulated TRIM50 resulted in both mRNA and protein depletion of SNAI1, and partially attenuated the epithelial–mesenchymal transition (EMT) induced by SNAI1. Results In this study, we demonstrate that TRIM50 is downregulated in human breast cancer and that its overexpression closely correlates with diminished invasion capacity in breast cancer, suggesting that TRIM50 may serve as a diagnostic marker and therapeutic target. Conclusion TRIM50 plays a key role in breast cancer proliferation and potentially serves as a prognostic and therapeutic target.

Naphthoquinone Derivatives from the Endophytic Fungus Fusarium solani Induce Pancreatic Cancer Cells Apoptosis via Targeting EGFR-Mediated PI3K/Akt Pathway.

Seven new polyketide compounds, four naphthoquinone derivatives, neofusarubins A-D (1, 3, 5, and 18) and three graminin-like compounds, fusofuranones A-C (19-21), together with 14 known naphthoquinone derivatives, were isolated from the solid fermentation of Fusarium solani, an endophytic fungus obtained from medicinal plant as tea, Camellia chrysantha. The structures of new compounds were elucidated based on chemical evidence and spectral data analysis (1D and 2D-NMR, HR-ESI-MS, ECD, SC-XRD). Among the isolated compounds tested, 2-acetonyl-3-methyl-5-hydroxy-7-methoxy-naphthazarin (11) exhibited the most potent inhibitory activity against pancreatic cancer in PANC-1, MiaPaCa-2, and BxPC-3 cells. Network pharmacology analysis revealed that compound 11 inhibited cell proliferation and promotion of apoptosis by targeting epidermal growth factor receptor (EGFR), which were confirmed by cellular thermal shift assay (CETSA), microscale thermophoresis (MST) and EGFR stably knockdown cells model assay, respectively. In addition, molecular mechanism studies in vitro showed that 11 could suppress the growth of pancreatic cancer cells by targeting EGFR and effectively inhibit downstream PI3K/Akt signaling pathway. Collectively, these findings provide a new EGFR targeting natural product for the treatment of pancreatic cancer.

Apoptotic Impact of Heliox Cold Plasma on a Cervical Cell Line Using Gold Nanoparticle-Doped Graphene Oxide Nanosheets

Background: Invasive cervical cancer is recognized as the second most common malignancy in women after breast cancer. Objectives: This study investigates, for the first time, the effect of gold nanoparticle-doped graphene oxide (GO) nanosheets on the human epithelial carcinoma (HeLa) cell line in the presence of heliox cold plasma. Methods: Graphene oxide nanosheets were synthesized using the Hummer method and then doped with gold nanoparticles. The nanoparticles were characterized by transmission electron microscopy (TEM), and the diffraction peaks of GO and gold nanoparticles were confirmed through X-ray diffraction (XRD) analysis. Additionally, the optical absorbance of the nanoparticles was measured in the range of 200 - 900 nm using UV-Visible spectroscopy. A plasma generator was fabricated to produce cold plasma using helium (He) and oxygen (O₂) gases at a 99:1 ratio. The radicals generated by the cold plasma were analyzed via optical emission spectroscopy (OES). Cell treatment was conducted by applying various concentrations of GO and GO/Au nanoparticles. Cellular phenotype was monitored through optical microscopy, and biocompatible concentrations of both nanoparticles were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Subsequently, cold plasma at varying distances and durations was applied to the nanoparticle-treated cells. The generated radicals and the expression of apoptotic genes in treated cells were assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and real-time PCR, respectively. Results: The width of the bacillus-like gold nanoparticles was 15.13 ± 0.96 nm. The cold plasma generated radicals such as N2I2⁺, N2II1⁻, He•, and O⁻•. XRD analysis confirmed the successful coupling of gold onto the GO nanosheets. The biocompatible concentrations of GO and GO/Au nanoparticles were found to be 30 µg/100 µL and 20 µg/100 µL, respectively, as determined by the MTT assay. Radical formation increased as incubation time was extended from 30 to 60 seconds. Furthermore, real-time PCR analysis demonstrated the highest levels of p53, Bax, and caspase 3/8 expression at a plasma exposure time of 60 seconds in the composite-treated group, while Bcl2 expression was significantly reduced. Conclusions: The findings suggest that the parameters of heliox cold plasma and the concentrations of GO/Au nanoparticles must be optimized to effectively induce apoptosis in cervical cancer cells.

LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer.

Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.

Netupitant Inhibits the Proliferation of Breast Cancer Cells by Targeting AGK

Background: Currently, there is a significant lack of effective pharmacological agents for the treatment of breast cancer. Acylglycerol Kinase (AGK), a lipid kinase, has been found to be aberrantly expressed in breast cancer and is closely associated with tumor proliferation, migration, and invasion. However, no clinical anti-tumor drugs specifically targeting this kinase have been developed. Methods: siRNA was utilized to knock down the AGK gene; CCK8 and colony formation assays were employed to evaluate the in vitro proliferative capacity of tumor cells. Molecular dynamics simulations and BIL assays were conducted to analyze drug binding affinity. Annexin V/PI staining was used to assess apoptotic phenomena; subcutaneous xenograft tumor experiments in nude mice were performed to confirm the in vivo anti-tumor efficacy of the drug. Results: Netupitant exhibited stable binding affinity for AGK and interacted with amino acids within the ATP-binding region of the enzyme. The IC50 values for the SK-BR-3 and MDA-MB-231 cell lines were determined as 16.15 ± 4.25 µmol/L and 24.02 ± 4.19 µmol/L, respectively; at a concentration of 2.5 µmol/L, Netupitant effectively inhibited clonogenic capacity in breast cancer cells; furthermore, treatment with 10 µmol/L significantly induced apoptosis in these cells. Doses of 50 mg/kg and 100 mg/kg Netupitant markedly suppressed growth rates of subcutaneous xenograft tumors in nude mice while also promoting apoptotic processes. Both in vivo and in vitro studies indicated that Netupitant could inhibit the activation of the PI3K/AKT/mTOR signaling pathway. Conclusions: By targeting AGK, Netupitant inhibits its kinase activity, which leads to reduced phosphorylation levels of PTEN, thereby suppressing the activation of the PI3K/AKT/mTOR signaling pathway and ultimately resulting in apoptosis in breast cancer cells.

Preferential activation of type I interferon-mediated antitumor inflammatory signaling by CuS/MnO2/diAMP nanoparticles enhances anti-PD-1 therapy for sporadic colorectal cancer.

Converting the "cold" tumor microenvironment (TME) to a "hot" milieu has become the prevailing approach for enhancing the response of immune-excluded/immunosuppressed colorectal cancer (CRC) patients to immune checkpoint blockade (ICB) therapy. During this process, inflammation accompanied by different kinds of chemokines/cytokines inevitably occurs. However, some activated inflammatory signals exhibit protumor potency. Therefore, strategies that preferentially activate antitumor inflammatory signaling rather than tumor-promoting signaling need to be developed. Herein, we constructed a STING agonist-loaded CuS/MnO2 bimetallic nanosystem, termed diAMP-BCM. BCM with an optimized Cu/Mn ratio efficiently promoted the activation of proinflammatory signaling, and in combination with the STING agonist diAMP, diAMP-BCM controllably activated tumoricidal inflammatory signaling in APCs. DiAMP-BCM can efficiently generate ROS and promote the activation of STING, which induces the apoptosis of cancer cells and promotes the recruitment of monocytes while facilitating the polarization of macrophages and maturation of DCs. MC38 and CT26 CRC models were established to evaluate the in vivo antitumor effects of diAMP-BCM. Combined with ICB therapy, diAMP-BCM enables the rebuilding of tumor milieus with efficient tumor growth inhibition and alleviation of T-cell exhaustion, particularly in distal tumors, in sporadic colorectal cancer therapy. This study established a nanoplatform to promote the preferential activation of antitumor inflammatory signaling, rebuild the T-cell repertoire and alleviate T-cell exhaustion to enhance cancer ICB immunotherapy.

Biochanin A Induces Apoptosis in MCF-7 Breast Cancer Cells through Mitochondrial Pathway and Pi3K/AKT Inhibition.

The study aimed to investigate the molecular mechanisms by which Biochanin A inhibits proliferation and induces apoptosis in breast cancer cells. Cultured MCF-7 cells were divided into four groups: Group 1-control, while Groups 2, 3, and 4 were treated with Biochanin A at different concentrations. After treatment, the cells were monitored, and morphological changes were examined after 24 h of incubation. The results showed that Biochanin A inhibited cell proliferation, increased reactive oxygen species formation, and induced apoptosis. Furthermore, western blot analysis revealed that Biochanin A-treated cells exhibited lower expression of the Bcl-2, p-PI3K and p-AKT and higher expression of proapoptotic genes, including Bax, Caspase-3, Caspase-9, and cytochrome c. Additionally, PCR array analysis indicated that the gene expression levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated, while the expression levels of p21, p27, and p53 were significantly upregulated. These results suggest that Biochanin A can suppress the viability of breast cancer cells and induce apoptosis via the mitochondrial pathway, along with inhibition of the Pi3K/Akt signaling pathway and modulation of cell cycle markers.

EXTH-61. TOWARDS A QUANTUM THERAPY FOR GLIOBLASTOMA: A NEW THERAPEUTIC PARADIGM IN MEDICINE

Abstract BACKGROUND A cell operates as an interconnected bioelectrical circuit, utilising electron transfer processes for intracellular communication, with cytochrome c (Cyt c) playing a pivotal role. The redox processes of Cyt c, occurring via electron tunnelling, are essential for its translocation into the cytosol and modulation of its conformation to bind apoptotic protease activating factor 1. This highlights the need for novel technologies capable of interacting with these processes at the atomic scale to control downstream effects and induce apoptosis in cancer cells. METHODS We demonstrate that ‘bio-nanoantennae’, when supplied with an electrical current, enable quantum biological tunnelling for electron transfer (QBET) and facilitate cellular apoptosis in patient-derived IDH wild-type glioblastoma from both the infiltrative tumour margin and proliferative core. The bio-nanoantennae were constructed from gold nanoparticles functionalised with reduced Cyt c and zinc porphyrin as a redox couple. RESULTS Electrical polarisation of these bio-nanoantennae via resonant alternating currents in preclinical glioblastoma cells led to decreased metabolic activity and reduced cell viability by oxidizing Cyt c, thus inducing cellular stress. No significant effect was observed in healthy human astrocyte counterparts. The cytosol localised bio-nanoantennae induced differential gene expression related to ion channels, apoptosis, cancer proliferation and tumour suppression upon activation, in tumour relative to astrocyte cell populations. The bio-nanoantennae were also tested in 3D glioblastoma spheroid models, showing similar effects, and in vivo studies demonstrated a significant reduction in glioblastoma xenograft tumour size. CONCLUSION We propose that bio-nanoantennae modulate the redox state of Cyt c under an electrical field through QBET. To validate this, we investigated the tunnel junction energy and plasmon resonance scattering, and developed a mathematical model to explain the system’s behaviour. This innovative wireless electrical–molecular nanodevice, capable of inducing cancer cell apoptosis, paves the way for further applications of quantum signalling as a new (non-pharmacological) therapeutic paradigm.

Renoprotective Effects of Brown-Strain Flammulina velutipes Singer in Chronic Kidney Disease-Induced Mice Through Modulation of Oxidative Stress and Inflammation and Regulation of Renal Transporters

Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function.

Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) Against Non-Small-Cell Lung Cancer: Elucidating Effective Ingredients and Mechanism of Action

Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) is derived from the dried pseudobulb of the orchid family plants Cremastra appendiculata (D.Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, or Pleione yunnanensis Rolfe, and has the properties of clearing heat, detoxification, resolving phlegm, and dispersing nodules. It is frequently used for the treatment of various malignant tumors in clinical practice, especially lung cancer. CPPP is divided into two commercial specifications in the market, Maocigu (MCG) and Bingqiuzi (BQZ). However, owing to a lack of appropriate research strategies, the active ingredients and molecular mechanisms involved have not yet been clarified. This study intended to discover the combination of effective anti-lung-cancer ingredients in CPPP and explore their potential mechanisms of action. In this study, UHPLC-MS fingerprints of MCG and BQZ were established separately. Inhibitory effects on the proliferative viability and migratory ability of A459 and H1299 cells were evaluated as pharmacodynamic indicators. GRA and BCA were used to determine spectrum–effect relationships. Next, the identification and analysis of components of drug-containing serum were performed using UHPLC-Q-Exactive Orbitrap MS. Then, the results of the two analyses were combined to jointly screen out the anti-lung-cancer candidate active monomers of CPPP, and their in vitro activities were verified. Afterward, all effective ingredient combinations of MCG (MCGC) and BQZ (BQZC) were prepared according to their contents in the original medicinal materials. Their anti-lung-cancer activities in vitro and in vivo were compared and verified. Finally, we used the human lung cancer cell line A549 and the Lewis tumor xenograft model to investigate how BQZC would influence autophagy and apoptosis processes and the mechanisms involved. Overall, 11 predominant anti-lung-cancer active ingredients from CPPP were screened. Next, MCGC and BQZC were prepared according to their contents in the original medicinal materials, respectively, and their anti-tumor effects were equivalent to those of the original materials in vitro and in vivo. We found that BQZC could inhibit lung cancer cell growth and induce protective autophagy and apoptosis in lung cancer cells by activating the AMPK–mTOR–ULK1/BMF signaling pathway. These results provide important evidence for the clinical application and deep development of CPPP against tumors.

Advances in smart nanotechnology-supported photodynamic therapy for cancer.

Cancer has emerged as a formidable challenge in the 21st century, impacting society, public health, and the economy. Conventional cancer treatments often exhibit limited efficacy and considerable side effects, particularly in managing the advanced stages of the disease. Photodynamic therapy (PDT), a contemporary non-invasive therapeutic approach, employs photosensitizers (PS) in conjunction with precise light wavelengths to selectively target diseased tissues, inducing the generation of reactive oxygen species and ultimately leading to cancer cell apoptosis. In contrast to conventional therapies, PDT presents a lower incidence of side effects and greater precision in targeting. The integration of intelligent nanotechnology into PDT has markedly improved its effectiveness, as evidenced by the remarkable synergistic antitumor effects observed with the utilization of multifunctional nanoplatforms in conjunction with PDT. This paper provides a concise overview of the principles underlying PS and PDT, while also delving into the utilization of nanomaterial-based PDT in the context of cancer treatment.

Dual targeting and bioresponsive nano-PROTAC induced precise and effective lung cancer therapy

Epigenetic regulation has emerged as a promising therapeutic strategy for lung cancer treatment, which can facilitate the antitumor responses by modulating epigenetic dysregulation of target proteins in lung cancer. The proteolysis-targeting chimera (PROTAC) reagent, dBET6 shows effective inhibition of bromodomain-containing protein 4 (BRD4) that exerts antitumor efficacy by degrading BRD4 via the ubiquitin-proteasome system. Nevertheless, the low tissue specificity and bioavailability impede its therapeutic effects and clinical translation on lung cancer treatment. Herein, we developed a type of dual targeting and bioresponsive nano-PROTAC (c R GD/L LC membrane/D S-P LGA/d B ET6, named RLDPB), which was constructed by using the pH and glutathione (GSH)-responsive polymer, disulfide bond-linked poly(lactic-co-glycolic acid) (PLGA-S-S-PLGA, DS-PLGA) to load the PROTAC agent dBET6, and further camouflaged with the homotypic LLC cell membranes, followed by the conjugation with cRGD ligand to the surface of the nanoparticles. Notably, RLDPB showed enhanced celluar uptake by lung cancer cells in vitro and accumulation in the tumors via the dual targeting structure including cRGD and LLC membrane. The pH/GSH responsiveness improved the release of dBET6 from the DS-PLGA-based nanoparticles within the cells. RLDPB was demonstrated to facilitate tumor regression by inducing the apoptosis of lung cancer cells with the degradation of BRD4. Thus, RLDPB can be considered a powerful tool to suppress lung cancer, which opens a new avenue to treat lung cancer by PROTAC.Graphical abstract

New Indole-based Phenylthiazolyl-2,4-dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent synthesis, cytotoxicity evaluation, and in silico studies.

A facile multicomponent synthesis of new indole-based phenylthiazolyl-dihydropyrazolone hybrids, their structural characterization, biological evaluation, and in silico investigations as anticancer agents are reported. Lead molecule 5i of the series showed potent activity against MCF-7 breast cancer cells with an IC50 of 3.92± 0.01µM while showing minimal toxicity to normal human lung cells (IC50 = 69.85 ± 3.95 µM). Further studies show that the compound exhibits antiproliferative activity by inducing apoptosis in MCF-7 cancer cells. The wound healing assay indicated impaired cell migration under the concentration-dependent dosage. The lead molecule 5i also successfully inhibited the tubulin polymerase enzyme with an IC50 of 4.16 ± 0.18 µM. A flow cytometric assay indicated compound 5i induced apoptosis through G0 phase cell cycle arrest. The binding mode and interactions of the compound with the tubulin were predicted by molecular modelling and calculating binding free energies. These findings explain the current series as a new class of microtubule polymerization inhibitors with anticancer activity suitable for developing anticancer agents targeting tubulin.