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Minor acidic glycans, such as sulfated and phosphorylated glycans, constitute only a small fraction of biological glycome, making their analysis a considerable challenge. In this study, we developed a technique to analyze minor acidic O-glycans in biological samples. First, efficient reaction conditions for the release of O-glycans from the proteins were determined. Next, a high-throughput method was established for the recovery of minor acidic glycans using NH2 spin columns. The performance of the established method was evaluated using mucin samples, and sulfated O-glycans were successfully detected in bovine submaxillary gland mucin and porcine stomach mucin. We also analyzed the minor acidic O-glycans in cultured cancer cells. In addition to trifucosylated sulfated O-glycans and disulfated O-glycans, sulfated O-glycans with KDN were detected in LS174T cells. The relative amount of sulfated glycans in LS174T cells was almost 10-fold higher than that in the other cells. Moreover, a large polylactosamine-type sulfated O-glycan with a molecular weight >3500 was detected in MKN45 cells. Interestingly, phosphorylated ribose, possibly bound to serine/threonine, was observed in all the cells used in this study. Thus, our established analytical method allows for the analysis of minor acidic O-glycans that cannot be detected using existing glycomics methods.

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Many cancer cells share with yeast a preference for fermentation over respiration, which is associated with overactive glucose uptake and breakdown, a phenomenon called the Warburg effect in cancer cells. The yeast tps1Δ mutant shows even more pronounced hyperactive glucose uptake and phosphorylation causing glycolysis to stall at GAPDH, initiation of apoptosis through overactivation of Ras and absence of growth on glucose. The goal of the present work was to use the yeast tps1Δ strain to screen for novel compounds that would preferentially inhibit overactive glucose influx into glycolysis, while maintaining basal glucose catabolism. This is based on the assumption that the overactive glucose catabolism of the tps1Δ strain might have a similar molecular cause as the Warburg effect in cancer cells. We have isolated Warbicin ® A as a compound restoring growth on glucose of the yeast tps1Δ mutant, showed that it inhibits the proliferation of cancer cells and isolated structural analogs by screening directly for cancer cell inhibition. The Warbicin ® compounds are the first drugs that inhibit glucose uptake by both yeast Hxt and mammalian GLUT carriers. Specific concentrations did not evoke any major toxicity in mice but increase the amount of adipose tissue likely due to reduced systemic glucose uptake. Surprisingly, Warbicin ® A inhibition of yeast sugar uptake depends on sugar phosphorylation, suggesting transport-associated phosphorylation as a target. In vivo and in vitro evidence confirms physical interaction between yeast Hxt7 and hexokinase. We suggest that reversible transport-associated phosphorylation by hexokinase controls the rate of glucose uptake through hydrolysis of the inhibitory ATP molecule in the cytosolic domain of glucose carriers and that in yeast tps1Δ cells and cancer cells reversibility is compromised, causing constitutively hyperactive glucose uptake and phosphorylation. Based on their chemical structure and properties, we suggest that Warbicin ® compounds replace the inhibitory ATP molecule in the cytosolic domain of the glucose carriers, preventing hexokinase to cause hyperactive glucose uptake and catabolism.

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Study of cell migration in cancer is crucial to the comprehension of the processes and factors that govern tumor spread. Cancer cells migrate invading tissues, causing alterations in cell adhesion, cytoskeleton, and signaling pathways. Little is known about the physical attributes of cancer cells that change when interacting with microenvironments. In this work, the local topography of the ECM has been mimicked through micropillar array substrates. MDA-MB-231 and MCF-7 breast cancer cells, exhibiting high and low metastatic potential, respectively, were analyzed. Differences in morphology and migration of the cells were investigated by examining the cell spreading area, circularity, aspect ratio, migration speed, and migration path. This work encountered that none of the studied cell lines have preferential orientation migrating on uniform patterns. In contrast, cell migration on graded patterns shows preferential orientation along the longitudinal direction from sparser to denser zones which is significantly influenced by substrate stiffness and indicates that both cell lines can sense the spacing gradient and respond to this topographical cue. The migration speed of the breast cancer cell lines significantly decreases from the sparse to medium to dense zones, registering higher values for the MDA-MB-231.

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Cell division is crucial for the survival of living organisms. Human cells undergo three types of cell division: mitosis, meiosis, and amitosis. The former two types occur in somatic cells and germ cells, respectively. Amitosis involves nuclear budding and occurs in cells that exhibit abnormal nuclear morphology (e.g., polyploidy) with increased cell size. In the early 2000s, Kirsten Walen and Rengaswami Rajaraman and his associates independently reported that polyploid human cells are capable of producing progeny via amitotic cell division, and that a subset of emerging daughter cells proliferate rapidly, exhibit stem cell-like properties, and can contribute to tumorigenesis. Polyploid cells that arise in solid tumors/tumor-derived cell lines are referred to as polyploid giant cancer cells (PGCCs) and are known to contribute to therapy resistance and disease recurrence following anticancer treatment. This commentary provides an update on some of these intriguing discoveries as a tribute to Drs. Walen and Rajaraman.

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Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography-mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC50 values ranging from 15.8 to 40.0 µg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph-mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties.

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Modern cancer diagnostics and treatment options have greatly improved survival rates; the illness remains a major cause of mortality worldwide. Current treatments for cancer, such as chemotherapy, are not cancer-specific and may cause harm to healthy cells; therefore, it is imperative that new drugs for cancer be developed that are both safe and effective. It has been found that lactic acid bacteria (LAB) have the potential to produce bacteriocins, which could potentially offer a promising alternative for cancer treatment. They have been shown in several studies to be effective against cancer cells while having no effect on healthy cells. More research is needed to fully understand the potential of LAB bacteriocins as anti-cancer medicines, to find the appropriate dose and delivery route, and to conduct clinical trials to evaluate the effectiveness and safety of the products in human patients, as is suggested by this work. Furthermore, LAB bacteriocins may evolve into a significant new class of anti-cancer drugs and food products. Patients with cancer may have a safe and effective alternative treatment option in the form of anti-cancer foods and drugs. Therefore, the aim of this study is to provide an in-depth analysis of the recent breakthroughs and potential future technical advancements of significant bacteriocins that are produced by LAB, how these bacteriocins function, and how these bacteriocins may be utilized as an anti-cancer agent. In addition, the current analysis emphasizes the significant constraints and boundaries that bacteriocins face when they are used as an anti-cancer factor.

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While most cancers are not transmissible, there are rare cases where cancer cells can spread between individuals and even across species, leading to epidemics. Despite their significance, the origins of such cancers remain elusive due to late detection in host populations. Using Hydra oligactis, which exhibits spontaneous tumour development that in some strains became vertically transmitted, this study presents the first experimental observation of the evolution of a transmissible tumour. Specifically, we assessed the initial vertical transmission rate of spontaneous tumours and explored the potential for optimizing this rate through artificial selection. One of the hydra strains, which evolved transmissible tumours over five generations, was characterized by analysis of cell type and bacteriome, and assessment of life-history traits. Our findings indicate that tumour transmission can be immediate for some strains and can be enhanced by selection. The resulting tumours are characterized by overproliferation of large interstitial stem cells and are not associated with a specific bacteriome. Furthermore, despite only five generations of transmission, these tumours induced notable alterations in host life-history traits, hinting at a compensatory response. This work, therefore, makes the first contribution to understanding the conditions of transmissible cancer emergence and their short-term consequences for the host.

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The emergence of calixarenes as versatile compounds in recent years marks a significant advancement in scientific research. In the area of analytical chemistry, calixarenes have garnered attention for their utility as selective chemosensors, enabling the sensitive and specific detection of metal ions through colorimetric and fluorimetric methods. Moreover, calixarenes have found applications in bioimaging, where they serve as effective probes for visualizing biological structures and processes with high resolution and sensitivity. Additionally, recent studies have explored the anticancer properties of calixarenes, unveiling their potential as therapeutic agents for cancer treatment. This comprehensive review explores recent advancements in calixarenes chemistry, emphasizing their significance in the colorimetric and fluorimetric detection of metal ions. Additionally, it highlights the mechanisms involved in chemosensor design, providing insights into the underlying principles driving their efficacy. Furthermore, the application of calixarenes in bioimaging, particularly for visualizing cellular structures and processes, is discussed, showing their potential in biomedical research and diagnostics. The anticancer activity of calixarenes and their derivatives is also explored, shedding light on their promising role as therapeutic agents. Through an extensive examination of recent literature, this review provides valuable insights into the multifaceted applications of calixarenes and offers perspectives for future research directions.

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OBJECTIVE: This study aimed to explore the expression and biological functions of SIRT3 in colorectal cancer cells (HCT-116), the impacts of sulforaphane on the ferroptosis of HCT-116 cells and the involvement of the SIRT3/AMPK/mTOR axis in those effects. METHODS: SIRT3-overexpressing (OE) and SIRT3-knockout (KO) cell lines were treated with different concentrations of sulforaphane, RSL-3, and IKE. Cell viability, intracellular ROS, MDA, iron levels, as well as mRNA and protein expressions of target genes were measured. RESULTS: SIRT3 expression in HCT-116 cells was increased by ferroptosis inducers and decreased by ferroptosis inhibitors. SIRT3 overexpression reduced cell viability and increased intracellular levels of ROS, MDA, and iron, whereas SIRT3 knockdown achieved the opposite effects. SIRT3 overexpression suppressed SLC7A11 expression and promoted the activation of AMPK/mTOR pathway. Restoration of SLC7A11 expression blocked the effects of SIRT3 on ferroptosis induction and cell viability inhibition. SIRT3 effects on cell viability and ferroptosis were antagonized by inhibitors of AMPK or mTOR. Moreover, sulforaphane triggered the ferroptosis of HCT-116 cells by activating the SIRT3/AMPK/mTOR axis. CONCLUSIONS: SIRT3 triggered SLC7A11-mediated ferroptosis in HCT-116 cells, reducing cell viability by activating the AMPK/mTOR pathway, and sulforaphane targets it to inhibit colorectal cancer.

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Multi-aptamer recognition of breast cancer cells (MCF-7) is utilized to achieve high specificity. The method comprises two parts, aptamer-functionalized mesoporous silica nanoparticles (MSNs) loaded with dissimilar dyes (thymolphthalein or curcumin) as signal transducers and aptamer-modified magnetic beads (MBs) as capture agents, which worked together to detect MCF-7 cells sensitively and accurately. The results indicated that the aptasensor has a linear detection range of 100 to 4000 cells and a detection threshold of 10 cells/mL. The method had been successfully employed to detect breast cancer cells in real blood samples to distinguish between breast cancer patients and healthy individuals. In conclusion, the development of the multi-aptamer-based colorimetric sensor offered a novel method for the highly selective detection of MCF-7 cells, contributing to the accurate identification of breast cancer.

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Royal jelly (RJ) is a natural food product with nutritional value and anticancer activity. However, their effects on gastric cancer are unclear. Here, we show that treatment with 5-320 µg/mL of RJ, ethanol extract (RJEE), and protein hydrolyzate (RJPH) decreased the viability of MKN-28 gastric cancer cells, with a half-maximal inhibitory concentration of 123.22 µg/mL for RJEE. RJ, RJEE, and RJPH increase the lactate dehydrogenase release rate and change the morphology of the cells, resulting in cell shrinkage, nucleoplasm condensation, and the formation of apoptotic bodies. RJ and its functional components stagnated the cell cycle in the G0/G1 phase, accompanied by the accumulation of reactive oxygen species, decreased mitochondrial membrane potential, and increased expression levels of p53 and p21 proteins, caspase-3 activation, and apoptosis. Therefore, RJ, RJEE, and RJPH have potential inhibitory effects on the proliferation of gastric cancer cells.

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Purpose: Erythrocytes and fibroblasts in the pancreatic cancer tumor microenvironment promote tumor cell growth and invasion by providing nutrients and promoting immunosuppression. Additionally, they form a barrier against the penetration of chemotherapeutic drugs. Therefore, the search for diversified tumor-targeting materials plays an essential role in solving the above problems. Methods: Physicochemical characterization of Graphene fluorescent nanoparticles (GFNPs) and nanomedicines were analyzed by transmission electron microscopy (TEM), elemental analyzers and ultraviolet fluorescence (UV/FL) spectrophotometer. Localization of GFNPs in cell and tissue sections imaged with laser confocal microscope, fluorescence scanner and small animal in vivo imager. Qualitative detection and quantitative detection of GFNPs and GFNPs-GEM were performed using High performance liquid chromatography (HPLC). Results: Based on the 3 nm average dimensions, GFNPs penetrate vascular endothelial cells and smooth muscle cells, achieve up to label 30% tumor cells and 60% cancer-associated fibroblasts (CAFs) cells, and accurately label mature red blood cells in the tumor microenvironment. In orthotopic transplanted pancreatic cancer models, the fluorescence intensity of GFNPs in tumors showed a positive correlation with the cycle size of tumor development. The differential spatial distribution of GFNPs in three typical clinical pancreatic cancer samples demonstrated their diagnostic potential. To mediate the excellent targeting properties of GFNPs, we synthesized a series of nanomedicines using popular chemotherapeutic drugs, in which complex of GFNPs and gemcitabine (GFNPs-GEM) possessed stability in vivo and exhibited effective reduction of tumor volume and fewer side effects. Conclusion: GFNPs with multiple targeting tumor microenvironments in pancreatic cancer possess diagnostic efficiency and therapeutic potential.

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Essential oils (EOs) which cover about 91% whole biomolecules formulated from Jasminum sambac leaves based on Gas chromatography-mass spectrometry were employed to identify structures. EOs were observed as good agents in the preparation of Silver nanoparticles (AgNPs) through the proposed mechanism that was attempted to interpret the pathway of the bio-preparation process. The characterization of EOs-AgNPs carried via ultraviolet-visible to reveal surface plasmon resonance at 420 nm, Fourier transform infrared to observe functional groups EOs compared to EOs-AgNPs. X-ray diffraction (XRD) revealed a broad chart owing to the small size of AgNPs in average size less than 10 nm calculated relying on image J software, spherical AgNPs with a small dispersive size observed by transmission electron microscopy. Quasi near spherical surface morphology of EOs-AgNPs had detected by field emission scanning electron microscope. EOs-AgNPs were assessed for their antibacterial potential against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria as suppressing bacterial agents. EOs-AgNPs had their anti-breast cancer MCF-7 cell line ability investigated by DNA fragmentation; cycle flow cytometry (apoptosis) at half maximal inhibitory concentration (IC50) was determined at 260 µg/mL which has been stated by cytotoxicity (MTT) assay. EOs-AgNPs have antibacterial and anticancer therapeutic potential, and it is safe, inexpensive, and scalable in the nanoscale range.

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G-quadruplex (G4) DNA structures are increasingly acknowledged as promising targets in cancer research, and the development of G4-specific stabilizing compounds may lay a fundamental foundation in precision medicine for cancer treatment. Here, we propose a light-responsive G4-binder for precise modulation of drug activation, providing dynamic and spatiotemporal control over G4-associated biological processes contributing to cancer cell death. We developed a specialized fluorinated azobenzene (AB) switch equipped with a quinoline unit and a positively charged carboxamide side chain, Q-Azo4F-C, designed for targeted binding to G4 structures within cells. Biophysical studies, combined with molecular dynamics simulations, provide insights into the unique coordination modes of the photoswitchable ligand in its trans and cis configurations when interacting with G4s. The observed variations in complexation processes between the two isomeric states in different cancer cell lines manifest in more than 25-fold reversible cytotoxic activity. Immunostaining conducted with the structure-specific G4 antibody (BG4), establishes a direct correlation between cytotoxicity and the varying extent of G4 induction regulated by the two isoforms. Finally, we demonstrate the photo-driven reversible regulation of G4 structures in lung cancer cells by Q-Azo4F-C. Our findings highlight the potential of light-responsive G4-binders in advancing precision cancer therapy through dynamic control of G4-mediated pathways.

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Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

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Lab-on-chips supported by hydrogel matrices are excellent solutions for cell culture; thus, this literature review presents examples of scientific research in this area. Several works are presenting the properties of biocompatible hydrogels that mimic the cellular environment published recently. Hydrogels can also be treated as cell transporters or as a structural component of microfluidic devices. The rapidly growing scientific sector of hydrogel additive manufacturing is also described herein, with attention paid to the appropriate mechanical and biological properties of the inks used to extrude the material, specifically for biomedical purposes. The paper focuses on protocols employed for additive manufacturing, e.g., 3D printing parameters, calibration, ink preparation, crosslinking processes, etc. The authors also mention potential problems concerning manufacturing processes and offer example solutions. As the novel trend for hydrogels enriched with several biocompatible additives has recently risen, the article presents examples of the use of high-quality carbon nanotubes in hydrogel research enhancing biocompatibility, mechanical stability, and cell viability. Moving forward, the article points out the high applicability of the hydrogel-assisted microfluidic platforms used for cancer research, especially for photodynamic therapy (PDT). This innovative treatment strategy can be investigated directly on the chip, which was first proposed by Jedrych E. et al. in 2011. Summarizing, this literature review highlights recent developments in the additive manufacturing of microfluidic devices supported by hydrogels, toward reliable cell culture experiments with a view to PDT research. This paper gathers the current knowledge in these intriguing and fast-growing research paths.

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BACKGROUND: Prostate cancer (PCa) is the most common urinary tumor with the highest incidence rate and the second among the leading causes of death worldwide for adult males. In the worldwide cancer incidence rate, PCa is on the increase. The cancerous cells in the prostate and cells in the microenvironment surrounding the tumor communicate through signal transduction, which is crucial for the development and spread of PCa. RECENT FINDINGS: Exosomes are nanoscale vesicles released into body fluids by various cells that can aid intercellular communication by releasing nucleic acids and proteins. Exosomes published by different types of cells in the tumor microenvironment can have varying impacts on the proliferation and growth of tumor cells via various signaling pathways, modes of action, and secreted cytokines. CONCLUSION: The main purpose of this review is to describe the effects of different cell-derived exosomes in the tumor microenvironment of PCa on the progression of tumor cells, as well as to summarize and discuss the prospects for the application of exosomes in the treatment and diagnosis of PCa.

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As a typical natural photosensitizer, hypocrellin B (HB) offers the advantages of high molar extinction coefficient, high phototoxicity, low dark toxicity, and fast metabolism in vivo. However, the lack of tumor specificity hinders its clinical applications. Herein, we designed and synthesized a glutathione (GSH) responsive photosensitizer based on HB. The 7 - nitro - 2,1,3 - benzoxadiazole (NBD) covalently connected to HB not only served as a fluorescence quenching group but also as a GSH activating group. The photosensitizer HB-NBD showed almost no fluorescence and singlet oxygen generation as a result of the photoinduced electron transfer between HB and NBD. The designed photosensitizer HB-NBD can be activated by GSH in solutions and cancer cells, and then obtain recuperative fluorescence and photosensitive activity.

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Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.