HSC-3 Cells Research Articles

IN VITRO ANTICANCER ACTIVITY OF HISTATIN-1 COMBINATION WITH CISPLATIN IN HEAD AND NECK CANCER CELL LINES.

Chemotherapy of head and neck squamous cell carcinoma (HNSCC) is associated with significant side effects. Antimicrobial peptides (AMPs), which are naturally occurring defense molecules like defensin-1 and LL-37 found in human secretions, have demonstrated potential in prompting tumor cell apoptosis and enhancing the effect of chemotherapeutic agents. However, the anticancer potential of histatin has not yet been thoroughly examined. The aim of the study was to explore the anticancer activity of histatin, an AMP present in human saliva and used alone or in combination with cisplatin in HNSCC cell lines. The gene expression of histatin was evaluated in the HSC4 and SCC25 cell lines by qRT-PCR. Cell proliferation was investigated at different concentrations of histatin peptide (His-1), cisplatin, and their combination using an MTT assay. SCC25 cells expressed both HTN1 (histatin-1) and HTN3 (histatin-3), whereas the HSC4 cell line expressed only HTN1. The combination of exogenous His-1 and cisplatin demonstrated a synergistic anti-proliferative effect against the HNSCC cell lines in a dosedependent manner. The combination of low-dose cisplatin and histatin inhibits HNSCC cell proliferation. His-1 sensitizes tumor cells to the cytotoxic effects of cisplatin potentially allowing for a reduction in its effective concentration.

Cydonia oblonga extract mediated biosynthesis of gold nanoparticles: Analysis of its anti-oral cancer and antioxidant properties

Here, using natural and biological macromolecules derived from Cydonia oblonga extract, we have developed a green protocol for the biogenic made Au NPs. Under ultrasonic activated conditions, the Cydonia oblonga phytomolecules were employed as an efficient green reducing agent for the Au3+ ions to the Au0 NPs. Additionally, by encapsulating or capping, they allowed the Au NPs to stabilize on their own. Several physicochemical techniques, such as elemental mapping, TEM, FE-SEM, UV–Vis spectroscopy, EDS, and ICP-OES, were used to analyze the structure of the Au NPs/Cydonia oblonga bio-nanocomposite. The field of medicinal therapeutics pertaining to human health includes cancer treatment as a major component. Subsequently, the as prepared Au NPs/Cydonia oblonga bio-nanocomposite was investigated for antioxidant and human anti-oral cancer assays. In such studies a number of cell lines, viz., HSC-3, HSC-2, and Ca9-22 were used in determining the cytotoxicity. Notably, Au NPs/Cydonia oblonga exhibit significant anti-oral cancer properties against HSC-3, HSC-2, and Ca9-22 cancer cell lines following time and dose-dependent manner. The corresponding IC50 values were determined as 201, 192, and 246 µg/mL respectively. DPPH radical scavenging method was used to determine the antioxidant activity of Au NPs/Cydonia oblonga bio-nanocomposite. The significant IC50 value suggested the material having very good antioxidant potential. The anti-human oral cancer effect of our material is believed to be due to its antioxidant effects.

Peptide-mediated targeting of Quantum Dots in a 3D model of head and neck cancer

BackgroundOral squamous cell carcinoma (OSCC) treatment mainly relies on surgery. The status of surgical margin is a major prognostic factor for patients as positive margins are associated with lower survival. However, the anatomical particularities of this area complicate margin establishment. Fluorescence guided surgery (FGS) could be employed as an intraoperative technique to improve tumor resection and margin investigation. Quantum dots (QDs) serve as ideal contrast agents in this technique due to their brightness and stability. Since αVβ6 integrin is overexpressed in OSCC, coupling QDs with A20FMDV2 peptide (QDs-A20) targeting the αVβ6 integrin constitute a real opportunity. This study investigates the accumulation of QDs-A20 in 2D and 3D tongue cancer models, as well as QDs coupled to a scrambled version of this peptide (QDs-Scr) or without peptide (QDs-SPP), for imaging purposes. MethodsCdSeCdS/ZnS quantum dots were coated with sulfobetaine polymers (QDs-SPP) and conjugated to A20FMDV2 peptide (QDs-A20) or its scrambled version (QDs-Scr). Two-dimensional (2D) and three-dimensional (3D) tongue cancer cells HSC-3 were employed to test the effectiveness of intracellular accumulation of all types of QDs. Targeting ability of each QDs was assessed by flow cytometry, while the depth of penetration into cancerous spheroids was assessed by fluorescence microscopy. ResultsQDs coating with sulfobetaines polymers (QDs-SPP) completely prevented their internalization by HSC-3 cells in 2D and 3D models, making QDs stealthy and preventing their non-specific accumulation. Conversely, peptides conjugated QDs (QDs-A20 & QDs-Scr) labeled HSC-3 monolayers and managed to label spheroid periphery up to 23 µm deep. However, no difference in accumulation was found between these two QDs whereas only A20 peptide could potentially target αVβ6 integrin. It appears that peptide conjugation increased QDs zeta potential, promoting their adsorption and subsequent endocytosis by cells, independently from αVβ6 integrin. ConclusionsThe present study highlighted the impact of peptide conjugation on QDs internalization in 2D and 3D tongue cancer cell models. QDs-SPP were stealthy and did not accumulate in cells. Peptides conjugated QDs could be used as contrast agents, but in a passive targeting approach. Modifications to surface chemistry are required to target αVβ6 integrin through active targeting. This study also highlights the need for controls such as scrambled peptides, the absence of which can lead to misinterpretation of results.

Inhibition of Oral Pathogenic Bacteria, Suppression of Bacterial Adhesion and Invasion on Human Squamous Carcinoma Cell Line (HSC-4 Cells), and Antioxidant Activity of Plant Extracts from Acanthaceae Family.

Medicinal plants have traditionally been used to treat various human diseases worldwide. In this study, we evaluated the leaf extracts of plants from the Acanthaceae family, specifically Clinacanthus nutans (Burm.f.) Lindau, Thunbergia laurifolia Lindl., and Acanthus ebracteatus Vahl., for their compounds and antioxidant activity. The ethanolic extracts of A. ebracteatus showed the highest total phenolic content at 22.55 mg GAE/g extract and the strongest antioxidant activities, with IC50 values of 0.24 mg/mL and 3.05 mg/mL, as determined by DPPH and ABTS assays. The antibacterial efficacy of these extracts was also tested against Streptococcus pyogenes, Streptococcus mutans, Staphylococcus aureus, and Klebsiella pneumoniae. The diameters of the inhibition zones ranged from 14.7 to 17.3 mm using the agar well diffusion method, with MIC and MBC values ranging from 7.81 to 250 mg/mL. Anti-biofilm formation, antibacterial adhesion, and antibacterial invasion assays further demonstrated that these medicinal plant extracts can inhibit bacterial biofilm formation and prevent the adhesion and invasion of oral pathogenic bacteria on the human tongue squamous cell carcinoma-derived cell line (HSC-4 cells). The ethanolic extracts of C. nutans and A. ebracteatus were able to inhibit the gtfD and gbp genes, which facilitate biofilm formation and bacterial adherence to surfaces. These findings provide new insights into the antibacterial and antioxidant properties of plant extracts from the Acanthaceae family. These activities could enhance the clinical and pharmaceutical applications of plant extracts as an alternative therapy for bacterial infections and a dietary supplement.

Okanin Inhibits Cell Growth and Induces Apoptosis and Pyroptosis in Oral Cancer.

Okanin, a flavonoid compound derived from Bidens pilosa L., has garnered attention for its anti-inflammatory properties. Although Bidens pilosa is commonly used in healthcare products and functional foods, the anticancer potential of okanin, particularly in oral cancer, remains underexplored. This study aims to investigate the effects of okanin on oral cancer cell lines and its potential as a therapeutic agent. The study involved assessing the cytotoxic effects of okanin on oral cancer cell lines SAS, SCC25, HSC3, and OEC-M1. The IC50 values were determined using methylene blue assays, and the clonogenic capacity was evaluated through colony formation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis. Caspase-3/7 activity assays and annexin V/7-AAD staining confirmed the induction of apoptosis and pyroptosis. In vivo efficacy was assessed using a SAS xenograft model, and immunohistochemical analysis of xenograft tissue was performed to examine pyroptosis-related markers. Okanin exhibited potent cytotoxic effects with IC50 values of 12.0 ± 0.8, 58.9 ± 18.7, 18.1 ± 5.3, and 43.2 ± 6.2 μM in SAS, SCC25, HSC3, and OEC-M1 cells, respectively. It caused dose- and time-dependent reductions in cell viability and significantly impaired clonogenic capacity. Flow cytometry revealed G2/M cell cycle arrest and increased sub-G1 population, indicating cell cycle disruption and death. Okanin induced both apoptosis and pyroptosis, as confirmed by caspase-3/7 activity and annexin V/7-AAD staining. In vivo, okanin reduced tumor growth and involved pyroptosis-related markers such as CASP1, GSDMC, GSDMD, and GSDME. Okanin demonstrates significant anticancer potential, particularly in oral cancer, by inducing both apoptosis and pyroptosis. Its efficacy in reducing tumor growth in vivo further supports its potential as a novel therapeutic option. Further mechanistic studies are needed to elucidate the pathways involved in okanin-mediated cell death and to explore its clinical applications.

Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites.

Cellular communication is regulated at the plasma membrane by the interactions of receptor, adhesion, signaling, exocytic,and endocytic proteins. Yet, the composition and control of these complexes in response to external cues remain unclear. We use high-resolution and high-throughput fluorescence imaging to map the localization of growth factor receptors and related proteins at single clathrin-coated structures in human squamous HSC3 cells. We find distinct protein signatures between control cells and cells stimulated with growth factors. Clathrin sites at the plasma membrane are preloaded with some receptors but not others. Stimulation with epidermal growth factor induces capture and concentration of epidermal growth factor, fibroblast growth factor1, and low-density lipoprotein receptor (EGFR, FGFR1, and LDLR). Regulatory proteins including ubiquitin ligase Cbl, the scaffold Grb2, and the mechanoenzyme dynamin2 are also recruited. Disrupting FGFR1 or EGFR activity with drugs prevents the recruitment of both EGFR and FGFR1. EGF was able to activate FGFR1 phosphorylation. Our data reveal novel coclustering and activation of receptors and regulatory factors at clathrin-coated sites in response to stimulation by a single growth factor, EGF or FGF. This behavior integrates growth factor signaling and allows for complex responses to extracellular cues and drugs at the plasma membrane of human cells.

Long non-coding RNA MAGEA4-AS1 binding to p53 enhances MK2 signaling pathway and promotes the proliferation and metastasis of oral squamous cell carcinoma

Long non-coding RNAs (lncRNAs) regulate the occurrence, development and progression of oral squamous cell carcinoma (OSCC). We elucidated the expression features of MAGEA4-AS1 in patients with OSCC and its activity as an OSCC biomarker. Furthermore, the impact of up-regulation of MAGEA4-AS1 on the cellular behaviors (proliferation, migration and invasion) of OSCC cells and intrinsic signal mechanisms were evaluated. Firstly, we analyzed MAGEA4-AS1 expression data in The Cancer Genome Atlas (TCGA) OSCC using a bioinformatics approach and in 45 pairs of OSCC tissues using qPCR. Then CCK-8, ethynyl deoxyuridine, colony formation, transwell and wound healing assays were conducted to assess changes in the cell proliferation, migration and invasion protential of shMAGEA4-AS1 HSC3 and CAL27 cells. The RNA sequence of MAGEA4-AS1 was identified using the rapid amplification of cDNA ends (RACE) assay. And whole-transcriptome sequencing was used to identify MAGEA4-AS1 affected genes. Additionally, dual-luciferase reporter system, RNA-binding protein immunoprecipitation (RIP), and rescue experiments were performed to clarify the role of the MAGEA4-AS1-p53-MK2 signaling pathway. As results, we found MAGEA4-AS1 was up-regulated in OSCC tissues. We identified a 418 nucleotides length of the MAGEA4-AS1 transcript and it primarily located in the cell nucleus. MAGEA4-AS1 stable knockdown weakened the proliferation, migration and invasion abilities of OSCC cells. Mechanistically, p53 protein was capable to activate MK2 gene transcription. RIP assay revealed an interaction between p53 and MAGEA4-AS1. MK2 up-regulation in MAGEA4-AS1 down-regulated OSCC cells restored MK2 and epithelial-to-mesenchymal transition related proteins’ expression levels. In conclusion, MAGEA4-AS1-p53 complexes bind to MK2 promoter, enhancing the transcription of MK2 and activating the downstream signaling pathways, consequently promoting the proliferation and metastasis of OSCC cells. MAGEA4-AS1 may serve as a diagnostic marker and therapeutic target for OSCC patients.

Effect of Agkistrodon acutus venom (AAVC-I) on apoptosis through modulation of the Keap1/Nrf2 pathway in HSC-3 oral squamous cell carcinoma cells.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions. Patients with OSCC exhibit a poor response to conventional chemoradiotherapies, which are associated with severe side effects. Therefore, it is essential to identify an effective therapeutic method to treat patients with OSCC. An anti-tumor compound, Agkistrodon acutus venom component I (AAVC-I), purified from Agkistrodon acutus venom, has demonstrated anticancer activity both in vitro and in vivo. However, the mechanism of AAVC-I's anticancer activity in cancer cells has yet to be established. This study aimed to investigate the mechanism of AAVC-I-induced apoptosis in HSC-3 OSCC cells and explore its regulatory effect on oxidative stress. Survival rates of human OSCC cell HSC-3 were detected by Cell Counting Kit-8 (CCK-8). The reactive oxygen species (ROS) level was analyzed by flow cytometry and fluorescence microscopy. The mitochondrial membrane potential was analyzed by cytometry and fluorescent microplate reader. Apoptosis of HSC-3 cells was analyzed using flow cytometry. The oxidative stress level was evaluated using glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits. In addition, the target proteins were analyzed by western blot. AAVC-I reduced HSC-3 cells' survival rates in a dose-dependent manner with a 50% inhibiting concentration (IC50) of 8.86 µg/mL. It induced apoptosis of HSC-3 cells and the expression of cleaved caspase-3, cleaved caspase-9, and Cyt-c increased significantly, whereas the expression level of Bcl-2 decreased in AAVC-I-treated HSC-3 cells. Thus, AAVC-I caused apoptosis of HSC-3 via the activation of the intrinsic apoptotic pathway. In addition, AAVC-I reduced the mitochondrial membrane potential in HSC-3, enhanced intracellular ROS, and increased intracellular oxidative stress levels in comparison to that of untreated control cells. Furthermore, AAVC-I increased the expression of Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) levels. These findings demonstrate the inhibitory effects and associated mechanisms of AAVC-I on the HSC-3 OSCC cell line. This insight could be valuable for investigating AAVC-I as a potential therapeutic option for patients with OSCC.

Elephantopus scaber Linn. Leaf Extract Sensitizes Doxorubicin in Inducing Apoptosis in HSC-3 Tongue Cancer Cells through Inhibiting Survivin Activity at Thr34

BACKGROUND: Previous research has demonstrated the effect of Elephantopus scaber Linn. leaf extract (ESLE) on various cancer cell lines. However, research on the effects of ESLE on oral squamous cell carcinoma (OSCC), especially tongue cancer, is still lacking. Moreover, the apoptotic mechanisms induced by ESLE are not well understood and require further exploration. Therefore, this study was conducted to investigate the effects of ESLE on cell viability and apoptosis in human squamous cell carcinoma (HSC)-3 tongue cancer cells.METHODS: HSC-3 cells were treated with varying concentrations of ESLE, doxorubicin, and a combination of both. Cell viability and apoptosis were assessed using MTT and Sub-G1 assays. The expression levels of survivin and its phosphorylated form at threonine (Thr)34 were evaluated using Western blot analysis.RESULTS: ESLE exhibited a concentration-dependent cytotoxic effect on HSC-3 cells in decreasing cell viability (Kruskal Wallis, p=0.001) and increasing apoptotic cells (ANOVA, p=0.001) significantly. When combined with doxorubicin, ESLE further enhanced the induction of apoptosis compared with doxorubicin alone. The combined treatment resulted in a decrease in the levels of phosphorylated survivin (p-Surv) Thr34, indicating the inhibition of survivin's anti-apoptotic function.CONCLUSION: ESLE significantly enhances the efficacy of doxorubicin, thereby sensitizing its ability to induce apoptosis in HSC-3 tongue cancer cells. This sensitization occurs through the inhibition of survivin activity, particularly at the Thr34 phosphorylation site. These findings suggest that ESLE could serve as a potential adjuvant to improve the effectiveness of doxorubicin in inducing apoptosis in tongue cancer cells.KEYWORDS: Elephantopus scaber, doxorubicin, tongue cancer, HSC-3 cells, apoptosis, Survivin, Thr34 phosphorylation

Multifunctional Bioactivity Electrospinning Nanofibers Encapsulating Emodin Provides a Potential Postoperative Management Strategy for Skin Cancer.

Skin cancer is threatening more and more people's health; its postoperative recurrence and wound infection are still critical challenges. Therefore, specialty wound dressings with multifunctional bioactivity are urgently desired. Emodin is a natural anthraquinone compound that has anti-cancer and anti-bacterial properties. Herein, we fabricated coaxial electrospinning nanofibers loaded with emodin to exploit a multifunctional wound dressing for skin cancer postoperative management, which encapsulated emodin in a polyvinylpyrrolidone core layer, combined with chitosan-polycaprolactone as a shell layer. The nanofibers were characterized via morphology, physicochemical nature, drug load efficiency, pH-dependent drug release profiles, and biocompatibility. Meanwhile, the anti-cancer and anti-bacterial effects were evaluated in vitro. The emodin-loaded nanofibers exhibited smooth surfaces with a relatively uniform diameter distribution and a clear shell-core structure; remarkably, emodin was evenly dispersed in the nanofibers with significantly enhanced dissolution of emodin. Furthermore, they not only display good wettability, high emodin entrapment efficiency, and biphasic release profile but also present superior biocompatibility and anti-cancer properties by increasing the levels of MDA and ROS in A-375 and HSC-1 cells via apoptosis-related pathway, and long-term anti-bacterial effects in a dose-independent manner. The findings indicate that the emodin-loaded nanofiber wound dressing can provide a potential treatment strategy for skin cancer postoperative management.

Design of Podophyllotoxin-based Hybrid Compounds as Potential Anticancer Agents

Background: Cancer has been regarded as the leading cause of death worldwide. Identifying new anti-neoplastics with high potency and low toxicity is urgent. Objective: Podophyllotoxin-based hybrid compounds were synthesized by esterification and characterized using NMR and HR-MS. In vitro cytotoxicity and molecular mechanism studies were performed. Methods: Podophyllotoxin was hybridized with three selected known natural compounds via esterification to develop candidates with increased biological activity or decreased toxicity. The CCK-8 assay, cell cycle analysis, AO/EB staining, immunofluorescent analysis, and molecular modeling were used for investigation. Results: Compound B4 displayed potent anticancer effect on HepG2 and HSC-2 cell lines, with IC50 values of 0.809 ± 0.183 and 0.267 ± 0.038 μM, respectively. Furthermore, B4 exhibited less antiproliferative activity in 293T cells with an IC50 value of 2.303 ± 0.216 μM. In addition, B4 demonstrated strong induction of S phase arrest and apoptosis, as well as demolished the microtubules in HSC-2 cells. Molecular docking study revealed that B4 could bind into the colchicine site of β-tubulin, as well as the interface of the α/β-tubulin dimer. Conclusion: Hybrid B4 exhibited potential anticancer activity, and further investigations can help in identifying novel lead molecules.

Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma

Purpose Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo. Methods MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo. Results In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect. Conclusion SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Given that the original tumor microenvironment of oral cancer cannot be reproduced, predicting the therapeutic effects of irradiation using monolayer cultures and animal models of ectopic tumors is challenging. Unique properties of carbon-ion irradiation (CIR) characterized by the Bragg peak exert therapeutic effects on tumors and prevent adverse events in surrounding normal tissues. However, the underlying mechanism remains unclear. The biological effects of CIR were evaluated on three-dimensional (3D) in vitro models of normal oral mucosa (NOMM) and oral cancer (OCM3 and OCM4) consisting of HSC-3 and HSC-4 cells. A single 10- or 20-Gy dose of CIR was delivered to NOMM, OCM3, and OCM4 models. Histopathological and histomorphometric analyses and labeling indices for Ki-67, γH2AX, and TUNEL were examined after CIR. The concentrations of high mobility group box 1 (HMGB1) were measured. NOMM exhibited epithelial thinning after CIR, which could be caused by the decreased presence of Ki-67-labeled basal cells. The relative proportion of the thickness of cancer cells to the underlying stroma in cancer models decreased after CIR. This finding appeared to be supported by changes in the three labeling indices, indicating CIR-induced cancer cell death, mostly via apoptosis. Furthermore, the three indices and the HMGB1 release levels significantly differed among the OCM4 that received different doses and with different incubation times after CIR while those of the OCM3 models did not, suggesting more radiosensitivity in the OCM4. The three 3D in vitro models can be a feasible and novel tool to elucidate radiation biology.

The impact of valproic acid administration: Effects on the growth of tongue cancer cells

Background: Tongue cancer represents the predominant malignancy within the oral cavity (25-40% of squamous cell carcinoma), necessitating treatment modalities such as surgery, radiotherapy, and chemotherapy. Valproic acid, an antiepileptic medication, functions as a histone deacetylase inhibitor or activator of anti-tumor signaling pathways. Objective: To deepen our understanding of the effects of valproic acid on the viability, cytotoxicity, proliferation, and migration capabilities of HSC-3 cells. Method: This study employed an in vitro laboratory approach, exposing HSC-3 cells to valproic acid. The experimental groups included a negative control with culture media devoid of valproic acid, and treatment groups exposed to valproic acid at concentrations of 145 ppm, 180 ppm, and 355 ppm, respectively. Results: Significant differences (p-value <0.05) were observed between HSC-3 cells treated with valproic acid (145 ppm, 180 ppm, and 355 ppm) and the control group in terms of viability, cytotoxicity, proliferation, and migration. Reduced cell viability, increased cytotoxicity, and decreased proliferation were noted. Migration assays indicated suppressed migration of HSC-3 cells. Conclusion: In summary, this study reveals that valproic acid exerts substantial effects on various aspects of HSC-3 cell behavior. It decreases cell viability, enhances cytotoxicity, suppresses proliferation, and inhibits cell migration. These findings highlight the potential of valproic acid as a therapeutic agent for tongue cancer by targeting crucial cellular processes involved in cancer progression. Further research and clinical trials are essential to confirm these effects and explore their application in cancer treatment strategies. Novelty/Originality of this article:: This study shows valproic acid has potential as a therapeutic agent for tongue cancer by decreasing cell viability, increasing cytotoxicity, suppressing proliferation, and inhibiting migration of HSC-3 cells. These findings introduce a new application of valproic acid as an anticancer agent, expanding the use of antiepileptic drugs. This study opens up opportunities for developing more effective tongue cancer therapies and encourages further research and clinical trials to validate these findings

Comparing the photodynamic treatment of OSCC between natural and artificial photosensitizers

Purpose: Since Verteporfin is the generally accepted photosensitizer for OSCC and other forms of skin cancer. Its synthetic structure and broad range in absorption has made it harmful to both tumor and healthy cells and tissues. The study aims to see whether a natural and herbal extract like Chlorophyllin, used in primarily bladder cancer, can become an alternative to Verteporfin. Methods: This study uses HSC-2 cell lines and mice models. The cancer cells in vitro and in vivo will be treated with increasing amounts and various durations of Chlorophyllin and Verteporfin. Killing in vitro is measured by MTT assay and in vivo is measured by xenograft tumor size. Positive control is Verteporfin, and negative control is DMSO in vitro or saline solution for the xenograft experiment. Possible results: The three main possible results: (1) Chlorophyllin kills more cancer cells in vitro and in vivo and it has less killed normal tissue. (5) Verteporfin kills more cancer cells but also has more damage to normal tissues when compared to Chlorophyllin. (8) Verteporfin kills more cancer cells in vitro and in vivo and it has less killed normal tissue. Conclusion: The results of the study will determine if natural alternatives are worth investing research into as they can be low-cost extraction, low toxicity, and high selectivity of cells to kill. Chlorophyllin can pave the way to more intensive research of natural photosensitizers in different types of cancers.

IL-37 attenuated HPV induced inflammation and growth of oral epithelial cells via regulating autophagy

This study investigated the impact of Human Papillomavirus (HPV) on inflammation and growth in oral epithelial cells, with a focus on the role of Interleukin-37 (IL37). Oral epithelial cells, including HOEC and HSC-3 cells, were employed in the research. The results revealed that HPV significantly induced inflammation in both types of oral epithelial cells, concurrently promoting cell growth and inhibiting apoptosis. IL37, a cytokine, was found to mitigate HPV-induced inflammation in oral epithelial cells. Moreover, IL37 counteracted HPV's effects on apoptosis and cell viability in oral epithelial cells. The study also identified a reduction in autophagy in HPV-infected oral epithelial cells, a phenomenon alleviated by IL37. Furthermore, chemical inhibition of autophagy was observed to attenuate HPV-induced inflammation and growth in oral epithelial cells. These findings contribute valuable insights into the pathogenesis of inflammation in oral epithelial cells associated with HPV and oral cancers, offering potential avenues for novel therapeutic strategies.

PRF Lysates Modulate Chemokine Expression in Oral Squamous Carcinoma and Healthy Epithelial Cells.

Platelet-rich fibrin (PRF), originally used to support soft tissue healing, is also considered a therapeutic option for treating oral lichen planus and leukoplakia. The progression from the two premalignant lesions to the aggressive malignant oral squamous cell carcinoma involves an inflammatory process linked to chemokine expression. Thus, there is a rationale for studying how PRF modulates the expression of chemokines in oral squamous carcinoma cells. To this aim, we expose the oral squamous carcinoma cell line HSC2 to IL1β and TNFα either alone or in the presence of lysates obtained from solid PRF membranes. We report here that in HSC2 cells, PRF lysates significantly reduce the forced transcription of chemokines, e.g., CXCL1, CXCL2, CXCL8, CXCL10, and CCL5. Moreover, PRF lysates attenuate the nuclear translocation of p65 in HSC2 oral epithelial cells when exposed to IL1β and TNFα. PRF lysates further reduce chemokine expression provoked by poly:IC HMW. Even though less pronounced, PRF lysates reduce IL1β- and TNFα-induced chemokine expression in TR146 cells. In primary oral epithelial cells, however, PRF lysates increase the basal expression of CXCL1, CXCL2 and CXCL8. Thus, PRF can exert a biphasic effect on chemokine expression in oral squamous cell carcinoma cell lines and primary oral epithelial cells. These findings suggest that PRF may reduce inflammation in a malignant environment while provoking an immunological response in healthy oral epithelium.

Silencing CK19 regulates ferroptosis by affecting the expression of GPX4 and ACSL4 in oral squamous cell carcinoma in vivo and in vitro

To analyze the mechanism of how interfering with the cytokeratin 19 (CK19) pathway via the ferroptosis pathway affects tumor biological behaviors in the process of oral squamous cell carcinoma (OSCC) development. TCGA was used to analyze the expression of CK19 in pan-cancer and head and neck squamous cell carcinoma (HNSC) and to explore the ferroptosis-related genes related to HNSC. The effect of silencing CK19 on the migration ability of HSC-4 cells was verified by wound healing and migration assay. HSC-4 cells with silencing of CK19 and tumor-bearing nude mouse model were constructed. RT-qPCR, immunofluorescence and western blot were used to analyze the expression of ferroptosis-related genes. CK19 is highly expressed in human OSCC and nude mice. The migration ability of cells in the CK19-silenced group was lower than that of the control group. In vivo and in vitro, CK19 was negatively correlated with the expression of ACSL4 and positively correlated with the expression of GPX4. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the CK19-silenced group. Silencing CK19 also increased intracellular Fe2+ content and MDA content. Silencing CK19 can affect the expression of GPX4 and ACSL4 to regulate ferroptosis and at the same time increase the content of MDA, Fe2+ and ROS levels, thereby activating the regulation of ferroptosis pathway in the development of OSCC.

Designed Mannosylerythritol Lipid Analogues Exhibiting Both Selective Cytotoxicity Against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells.

Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-β-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.

Progress on the effects and underlying mechanisms of evodiamine in digestive system diseases, and its toxicity: A systematic review and meta-analysis

BackgroundEvodiamine (EVO) is one of the primary components of Evodia rutaecarpa and has been found to have a positive therapeutic effect on various digestive system diseases. However, no systematic review has been conducted on the research progress and mechanisms of EVO in relation to digestive system diseases, and its toxicity. PurposeThis study aimed to provide a reference for future research in this field. Study designA systematic review and meta-analysis of the research progress, mechanisms, and toxicity of EVO in the treatment of digestive system diseases. MethodsFive electronic databases were utilized to search for relevant experiments. We conducted a comprehensive review and meta-analysis of the pertinent literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). ResultsEVO's animal experiments in digestive system diseases primarily focus on colorectal cancer, gastric ulcers, liver cancer, liver fibrosis, ulcerative colitis, colitis-associated cancer, and functional gastrointestinal disorders. EVO also has positive effects on pancreatic cancer, radiation enteritis, gastric cancer, tongue squamous cancer, hepatitis B, oral cancer, and esophageal cancer in vivo. EVO's in cellular experiments primarily focus on SGC7901, HT29, HCT-116, and HepG2 cells. EVO also exhibits positive effects on SW480, LoVo, BGC-823, AGS, COLO-205, MKN45, SMMC-7721, Bel-7402, QGY7-701, PANC-1, SW1990, BxPC-3, HSC4, MC3, HONE1, and CNE1 cells in vitro. The potential common pathways include TGF-β, PI3K-AKT, Wnt, ErbB, mTOR, MAPK, HIF-1, NOD-like receptor, NF-κB, VEGF, JAK-STAT, AMPK, Toll-like receptor, EGFR, Ras, TNF, AGE-RAGE, Relaxin, FoxO, IL-17, Hippo, and cAMP. The mechanisms of EVO on ulcerative colitis, gastric cancer, and HCT116 cells are still controversial in vivo. EVO may have a bidirectional regulatory effect on functional gastrointestinal disorders through calcium signaling. The mechanisms of EVO on HCT116, HT29, SW480, AGS, COLO-205, and SW1990 cells are still controversial in vitro. The question of whether EVO has obvious toxicity is controversial. ConclusionIn both cellular and animal experiments, EVO has demonstrated positive impacts on digestive system diseases. Nevertheless, additional in vivo and in vitro research is required to confirm the beneficial effects and mechanisms of EVO on digestive system diseases, as well as its potential toxicity.