Oral Squamous Carcinoma Research Articles

Effect of hinokitiol in ameliorating oral cancer: in vitro and in silico evidences.

The study aimed to evaluate the anticancer potential of hinokitiol in treating oral cancer by using in vitro models and examining its interaction with the Pim-1 protein through in silico methods. Hinokitiol was applied to KB-1 oral squamous carcinoma cells, where the half-maximal inhibitory concentrations (IC50) was determined. Morphologic changes in treated cells were observed using phase contrast microscopy, while acridine orange/ethidium bromide (AO/EB) staining was used to assess nuclear changes and apoptosis. Flow cytometry was employed to analyze the cell-cycle progression. Given the high expression of Pim-1 in oral squamous carcinoma cells, molecular docking and simulation were performed to evaluate hinokitiol's binding affinity and stability with the Pim-1 protein. To compare its effects, hinokitiol was also tested on non-cancerous pre-adipocytes (3T3-L1), providing insights into its selective cytotoxicity between healthy and cancerous cells. Hinokitiol treatment resulted in cytotoxic effects on KB-1 oral squamous carcinoma cells, with an IC50 of 30µg/mL after 24 and 48hs of exposure. Morphologic studies showed reduced cell population and density. In contrast, hinokitiol exhibited lower toxicity and caused fewer morphological changes in non-cancerous 3T3-L1 pre-adipocytes. Apoptosis was confirmed through acridine orange/ethidium bromide staining, while flow cytometry revealed cell-cycle arrest in the Synthesis phase (S) and Gap 2 phase/ Mitosis Phase (G2/M) phases. Molecular docking showed strong binding of hinokitiol to Pim-1, and simulations confirmed the interaction's stability. These findings suggest hinokitiol selectively targets cancer cells and effectively inhibit Pim-1, supporting its potential as an oral cancer treatment.

Multifunctional Temporary Dental Nanofillers Enhanced with Synergistically Active Chlorine-Containing Molecules against Streptococcus mutans and Its Effects on Oral Epithelial Cells.

Temporary dental fillers are critical for safeguarding teeth during the period between caries removal and permanent restoration. However, conventional fillers often lack sufficient antimicrobial properties to prevent bacterial colonization. To address this issue, the study researches on the development of antimicrobial Temporary Dental Nano-Fillers (TDNF) capable of targeting multiple cariogenic pathogens, including Streptococcus mutans, Lactobacillus casei, Candida albicans, and mixed-species planktonic cells/biofilms, which play a significant role in the progression of dental caries. The TDNF was formulated using a combination of Chloramine-T (CRT) and Cetylpyridinium Chloride (CPC), both known for their antimicrobial efficacy, and embedded in a nanoparticle matrix of hydroxyapatite (HAP) and silicon dioxide (SiO2). The synergistic antimicrobial effect of CRT and CPC, with MIC90 values of 12.5 and 6.25 ppm, respectively, displayed potent activity against S. mutans. Proteomic analysis, including gene ontology and protein-protein interaction network evaluations, further confirmed significant disruptions in S. mutans metabolic and stress response pathways, highlighting the bactericidal effectiveness of the formulation against S. mutans. Additionally, the formulation demonstrated sustained antimicrobial efficacy against other cariogenic pathogens such as L. casei, C. albicans and mixed-species planktonic cells and biofilms over a 16-day period. The TDNF (HAP+SiO2+CRT+CPC matrix) exhibited superior mechanical properties with a compressive strength of 237.7 MPa, flexural strength of 124.3 MPa, and shear bond strength of 52 MPa. Biocompatibility tests conducted on human oral squamous carcinoma cells (OECM-1) indicated over 95% cell viability, affirming its safety for preclinical or clinical applications. The multifunctional TDNF developed in this study successfully combines mechanical reinforcement with broad-spectrum antimicrobial efficacy, offering a promising interim solution in dental restorations. Its ability to protect against microbial colonization, while maintaining structural stability, positions it as an effective temporary material that enhances patient outcomes during the period before permanent restoration.

Potential pro-tumour cytokine in oral squamous cellular carcinoma: IL37.

Inflammation and immunosuppression are important features of tumours, including oral squamous cellular carcinoma (OSCC). Interleukin 37 (IL37), a cytokine known for the ability to suppress inflammation and immunity, shows two seemingly contradictory functions in tumours. This study aims to investigate the mechanism that regulates IL37 and its role in OSCC progression. Herein, IL37, CD86 and CD206 in OSCC specimens were determined. Hypoxia, MCC950 and siRNA-Gasdermin D (GSDMD) were utilised to investigate the mechanism of IL37 production and release. Animal experiments were established to examine the role of IL37 in OSCC growth invivo. We found the levels of IL37 are elevated in OSCC tissues compared with normal oral mucosa. In cell experiments, hypoxia was proved to be a vital facilitator in IL37 expression and release. Mechanically, hypoxia promoted IL37 expression through the activation of NACHT-LRR-PYD-containing protein 3 (NLRP3) inflammasome, and promoted IL37 release via GSDMD. Furthermore, IL37 levels in OSCC specimens are positively correlated with the number of M2 macrophages, but negatively with M1. Further studies revealed IL37 facilitated OSCC progression via promoting macrophage polarization from M1 to M2 and enhancing tumour cell proliferation. Thus, IL37 could be a promising target for OSCC treatment in the future.

Integrating clinical and genomic landscape analysis of perineural invasion identify ACTA1 as an oncogene for oral squamous cell carcinoma.

Perineural invasion (PNI) has been shown to be a key pathological feature of several types of cancer, including oral squamous epithelial carcinoma (OSCC). However, the overall clinical and genomic landscape of PNI+ OSCC are still unclear, and the molecular mechanism of PNI remains to be further investigated. 279 OSCC samples were extracted from the TCGA database and grouped according to PNI. The clinicopathological information, prognostic and survival analyses were performed. The Cibersort algorithm and ESTIMATE algorithm was used to estimate the impacts on proportion of immune cells, immune score and stromal score by PNI. Immunotherapy prediction analysis was also performed. 167 differentially expressed genes were screened for functional enrichment analysis. Actin α1 (ACTA1) protein, which was significantly upregulated in the PNI+ group, was selected for validation in our OSCC patient's cohort (n = 70). We next analyzed the ratio and absolute number of key immunocytes in peripheral blood of OSCC patients according to Actin α1 expression by flow cytometry. PNI was more likely to occur in patients with advanced tumors and worse prognosis. Immunomodulation analyses showed that T cells follicular helper and cells were significantly lower, but M2 macrophages and total stromal score was significantly higher in PNI+ OSCC. Immunotherapy prediction analyses showed that PNI+ OSCC may be more sensitive to CTLA4 inhibitor treatment. 167 differentially expressed genes were identified and enriched in muscle structure and cell movement-related pathway. Among them, Actin α1 (ACTA1) was significantly upregulated in PNI+ advanced OSCC with worse clinical outcome whose had relatively low ratio of CD3+CD8+ circulating cytotoxic T cells. PNI+ OSCC patients with upregulated of Actin α1 could benefit from cytotoxic T cell-mediated immunotherapy.

Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Oral Cancers: A Retrospective Analytical Study.

Introduction Head and neck cancers account for 30% of malignancies in India and oral squamous cell carcinoma is most common. 80% of the patients present with locally advanced disease and many of them are inoperable. In this study we documented the outcomes of neoadjuvant chemotherapy (NACT) in locally advanced oral cancer staged T4 with regards to downstaging the disease and to make the tumor more amenable for surgery with better access. The objectives of the study are to document the outcomes of NACT in patients with locally advanced oral cancers and to correlate the response to NACT and adequacy of resection by histopathology examination of the specimen. Methodology Clinical data of 96 patients with locally advanced squamous cell carcinoma of the oral cavity staged T4a and T4bwho received two cycles of NACT between December 2018 and November 2022 were reviewed respectively and the outcomes and response following NACT were documented. Results Among 96 patients in this study, 68 (70.9%) patients were staged T4a and 28 (29.1%) were staged T4b. 31 (30.2%) patients showed partial response, 36 (37.5%) had stable disease and 29 (30.2%) had progressive disease following 2 cycles of NACT. All patients underwent definitive surgery following NACT and were followed up for 14 months. Among those staged T4a, 12 patients (33.3%)had close margins, eight patients (34.8%) had positive margins and 10 patients (16.2%) had a recurrence. Among those staged T4b, 24 patients (66.7%) had close margins (less than 5mm distance after formalin fixation), 15 patients (65.2%) had positive margins while 17 patients (60.7%) had a recurrence in the 14 month follow-up period. Conclusion NACT makes tumors more amenable for surgery in locally advanced oral squamous carcinoma. However, 30% of patients do not respond to it.

Phyto-mediated biosynthesis of silver nanoparticles using Aloe barbadensis Miller leaves gel with improved antibacterial, anti-fungal, antioxidant, anti-inflammatory, anti-diabetic, and anti-cancer activities

An effective topical therapeutic agent requires a multifunctional attribute such as antibacterial, antioxidant, and anti-inflammatory efficacy. The green-synthesized metallic and metallic oxide nanoparticles have shown significant applicability in this regard. Hence a biosynthesis of silver nanoparticles (AgNPs) using Aloe barbadensis miller leaf gel was fabricated and evaluated for effect of imperative influences such as temperature, time, and concentration of reactant on AgNPs synthesis. Furthermore, the biomimetic qualities were assessed to ensure the safety and efficacy. The synthesis of stabilized and capped AgNPs presented a UV–vis–based plasmonic resonance at ∼ 400 nm. The reduction of silver nitrate was further confirmed by the shift in FTIR spectra for -OH around 2870 cm−1. SEM and TEM images revealed cubic shape of the AgNPs. Whereas X-ray diffraction pattern indicated crystalline structure (crystallite size of ∼ 31.14 nm) with an inter-planar spacing value of 2.77, 1.96, and 1.67 Å for (200), (220), and (311) planes, respectively. In addition, AgNPs indicated a steady dispersion, homogeneity, and strong anionic zeta potential (∼ 35.4 mV). The results of antibacterial and antifungal activity demonstrated the potential of phyto-synthesized AgNPs in mitigation of infection associated with tested bacterial strain Bacillus subtilis, Bacillus megaterium, Shigella flexneri, Trichoderma viride, Aspergillus niger, and Penicillium crysogenum. Moreover, the results of hydrogen peroxide-based scavenging, anti-inflammatory, and anti-diabetic study revealed that the biosynthesized AgNPs exhibit an improved biomimetic attribute. Additionally, the biocompatibility assay demonstrated > 80 % of CaCO-2 and L-929 cells viability at 1.67 μg/mL and 3.35 μg/mL, respectively. The anticancer activity of synthesized AgNPs against epithelium-like phenotype oral squamous carcinoma cells (CLS-354/WT) displayed IC50 of 11.58 μg/mL. The results indicate that biogenic produced AgNPs may find suitable use as a potential therapeutic agent due to multifunctional attribute.

Cancer Cell-Selective Inhibition of Migration by Styrenic Catiomer Emulsions.

Cancer metastasis remains the most formidable cause of mortality and morbidity in cancer patients. Developing an effective and economical method toward cancer antimetastatic strategy demands immediate attention in anticancer therapy. Herein, we followed a cost-effective greener method for preparing a small family of amphiphilic catiomers with varied styrene content (45, 63, and 83%), which revealed the unique potential of promoting normal cell migration while retarding cancer metastasis. The styrenic polymers formed micellar self-assembly in aqueous phase and exhibited a cationic charge. Polymers were quite nontoxic up to 200 μg/mL concentration toward human embryonic kidney cell HEK293 as well as human, triple negative breast cancer cell MDAMB-231, mouse melanoma cell B16F10, and human oral squamous carcinoma cell FaDu. Confocal imaging and fluorescence activated cell sorting (FACS) showed effective incorporation of polymers within cells. Interestingly, the polymer-treated HEK293 cells underwent prominent wound healing in scratch assay. However, the as-synthesized polymer-treated cancer cells resisted migration as analyzed from the scratch assay. A mechanistic study using immunoblotting assay established upregulation of migratory proteins vimentin and TGF-β and downregulation of E-cadherin in normal HEK293 cells. Remarkably, this trend was completely reversed in cancer cell MDAMB-231. This study describes the extraordinary potential of styrenic catiomers as wound healers for normal cells while inhibiting cancer metastasis.

Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model.

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.

Dual inhibition of topoisomerase II and microtubule of podophyllotoxin derivative 5p overcomes cancer multidrug resistance

Compound 5p is a 4β-N-substituted podophyllotoxin derivative, which exhibited potent activity toward drug-resistant K562/A02 cells and decreased MDR-1 mRNA expression. Here, we further investigated its detail mechanism and tested its antitumor activity. 5p exerted catalytic inhibition of topoisomerase IIα, and didn’t show the inhibitor of topoisomerase I. 5p exhibited the inhibitory effect on microtubule polymerization. 5p showed potent anti-proliferation against breast cancer, oral squamous carcinoma, and their drug-resistant cell lines, with resistance index of 0.61 and 0.86, respectively. 5p downregulated the expression levels of P-gp in KBV200 cells and BCRP in MCF7/ADR cells in dose-dependent manner. Moreover, 5p induced KB and KBV200 cells arrest at G2/M phase by up-regulating the expression of γ-H2AX, p-Histone H3 and cyclin B1. 5p induced apoptosis and pyroptosis by increased the expression levels of cleaved-PARP, cleaved-caspase3, N-GSDME as well as LDH release in KB and KBV200 cells. In addition, 5p efficiently impaired tumor growth in KB and KBV200 xenograft mice. Conclusively, this work elucidated the dual inhibitor of topoisomerase II and microtubule of 5p and its mechanism of overcoming the multidrug resistance, indicating that 5p exerts the antitumor potentiality.

Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer.

The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.

Development and validation of accelerated failure time model for cause-specific survival and prognostication of oral squamous cell carcinoma: SEER data analysis.

Oral Squamous Cell Carcinoma is the most prevalent malignancies affecting the oral cavity. Despite progress in studies and treatment options its outlook remains grim with survival prospects greatly affected by demographic and clinical factors. Precisely predicting survival rates and prognosis plays a role in making treatment choices for the best achievable overall health outcomes. To develop and validate an accelerated failure time model as a predictive model for cause-specific survival and prognosis of Oral Squamous Cell Carcinoma patients and compare its results to the traditional Cox proportional hazard model. We screened Oral cancer patients diagnosed with Squamous Cell Carcinoma from the Surveillance Epidemiology and End Results (SEER) database between 2010 and 2020. An accelerated failure time model using the Type I generalized half logistic distribution was used to determine independent prognostic factors affecting the survival time of patients with oral squamous carcinoma. In addition, accelerated factors were estimated to assess how some variables influence the survival times of the patients. We used the Akaike Information Criterion, Bayesian Information Criterion to evaluate the model fit, the area under the curve for discriminability, Concordance Index (C-index) and Root Mean Square Error and calibration curve for predictability, to compare the type I generalized half logistic survival model to other common classical survival models. All tests are conducted at a 0.05 level of significance. The accelerated failure time models demonstrated superior effectiveness in modeling (fit and predictive accuracy) the cause-specific survival (CSS) of oral squamous cell carcinoma compared to the Cox model. Among the accelerated failure time models considered, the Type I generalized half logistic distribution exhibited the most robust model fit, as evidenced by the lowest Akaike Information Criterion (AIC = 27370) and Bayesian Information Criterion (BIC = 27415) values. This outperformed other parametric models and the Cox Model (AIC = 47019, BIC = 47177). The TIGHLD displayed an AUC of 0.642 for discrimination, surpassing the Cox model (AUC = 0.544). In terms of predictive accuracy, the model achieved the highest concordance index (C-index = 0.780) and the lowest root mean square error (RMSE = 1.209), a notable performance over the Cox model (C-index = 0.336, RMSE = 6.482). All variables under consideration in this study demonstrated significance at the 0.05 level for CSS, except for race and the time span from diagnosis to treatment, in the TIGHLD AFT model. However, differences emerged regarding the significant variations in survival times among subgroups. Finally, the results derived from the model revealed that all significant variables except chemotherapy, all TNM stages and patients with Grade II and III tumor presentations contributed to the deceleration of time to cause-specific deaths. The accelerated failure time model provides a relatively accurate method to predict the prognosis of oral squamous cell carcinoma patients and is recommended over the Cox PH model for its superior predictive capabilities. This study also underscores the importance of using advanced statistical models to improve survival predictions and outcomes for cancer patients.

Derived Neutrophils to Lymphocyte Ratio Predicts Survival Benefit from TPF Induction Chemotherapy in Local Advanced Oral Squamous Cellular Carcinoma.

This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan-Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018-1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000-1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002-1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010-1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC.

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.

Impact of Juglone, a PIN1 İnhibitor, on Oral Carcinogenesis Induced by 4-Nitroquinoline-1-Oxide (4NQO) in Rat Model.

Background and Objectives: PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. Materials and Methods: 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg/kg/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. Results: Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. Conclusions: The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.

Cosmos caudatus Leaf Extract Triggers Apoptosis of HSC-3 Cancer Cells by Decreasing Bcl-2 and Increasing Bax

BACKGROUND: Previous studies have demonstrated that Cosmos caudatus leaf extract (CCLE) exhibits cytotoxic effects against various types of human cancer. However, the CCLE cytotoxic effect towards oral squamous cell carcinoma (OSCC) cells has not been investigated. Therefore, this study was conducted to evaluate the effect of CCLE towards the viability and apoptosis in human oral squamous carcinoma (HSC)-3 cells.METHODS: HSC-3 cells were treated with various concentrations of CCLE for 24 h. The number of viable HSC-3 cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), meanwhile the apoptotic HSC-3 cells were measured using sub-G1 assay. Mitochondrial membrane potential was measured using flow cytometry. Bcl-2 and Bax protein content of HSC-3 cells were measured using enzyme-linked immunosorbent assay (ELISA).RESULTS: CCLE treatment could decrease the number of HSC-3 viable cells and increase the percentage of HSC-3 apoptotic cells in concentration-dependent manner. In mitochondrial membrane potential assay, CCLE-treated group displayed a peak shifment from 104 to 103. Bcl-2 protein contents of CCLE-treated group were decrease in concentration-dependent manner, meanwhile Bax protein contents of CCLE-treated group were increase in concentration-dependent manner.CONCLUSION: CCLE could trigger apoptosis in HSC-3 cells by decreasing Bcl-2 protein content and increasing Bax protein content in concentration-dependent manner, leading to intrinsic apoptotic pathway.KEYWORDS: Cosmos caudatus, HSC-3, apoptosis, mitochondrial membrane potential, Bcl-2, Bax

Piperine-coated zinc oxide nanoparticles target biofilms and induce oral cancer apoptosis via BCl-2/BAX/P53 pathway

BackgroundDental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations.MethodsWe synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells.ResultsZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53.ConclusionsThis approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice.

Arsenic Nanoparticles Trigger Apoptosis via Anoikis Induction in OECM-1 Cells.

Arsenic compounds have been used as therapeutic alternatives for several diseases including cancer. In the following work, we obtained arsenic nanoparticles (AsNPs) produced by an anaerobic bacterium from the Salar de Ascotán, in northern Chile, and evaluated their effects on the human oral squamous carcinoma cell line OECM-1. Resazurin reduction assays were carried out on these cells using 1-100 µM of AsNPs, finding a concentration-dependent reduction in cell viability that was not observed for the non-tumoral gastric mucosa-derived cell line GES-1. To establish if these effects were associated with apoptosis induction, markers like Bcl2, Bax, and cleaved caspase 3 were analyzed via Western blot, executor caspases 3/7 via luminometry, and DNA fragmentation was analyzed by TUNEL assay, using 100 µM cisplatin as a positive control. OECM-1 cells treated with AsNPs showed an induction of both extrinsic and intrinsic apoptotic pathways, which can be explained by a significant decrease in P-Akt/Akt and P-ERK/ERK relative protein ratios, and an increase in both PTEN and p53 mRNA levels and Bit-1 relative protein levels. These results suggest a prospective mechanism of action for AsNPs that involves a potential interaction with extracellular matrix (ECM) components that reduces cell attachment and subsequently triggers anoikis, an anchorage-dependent type of apoptosis.

Radiology-Pathology Concordance and Prognostication of Nodal Features in pN+ Oral Cavity Cancer.

The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC). pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter-rater kappa for radiologic nodal features was assessed in 100 randomly selected cases. Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN- (p = 0.006), iENE+ versus iENE- (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter-rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively. Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image-identified nodal features is high and their prognostic values are retained in pN+ OSCC. Level 3 (retrospective review comparing cases and controls) Laryngoscope, 2024.

Apigenin suppresses the low oxaliplatin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells via LINC00857.

Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is commonly utilized for cancer treatment as a platinum-based chemotherapy drug. However, the utilization of low-dose OXA carries the risk of inducing epithelial-mesenchymal transition (EMT) in cancer cells and promoting tumor metastasis, thereby giving rise to potential side effects. The purpose of this study is to investigate the synergistic inhibitory effect of apigenin and OXA and its potential mechanism. HSC-3 cells of oral squamous carcinoma cells (OSCCs) were divided into control, apigenin-treated and co-treated groups. A wound healing assay was conducted to assess alterations in cellular motility and migration, an invasion assay was performed to assess invasiveness, and a three-dimensional culture assay was employed to evaluate angiogenic capacity. Cultured cells were utilized for total DNA extraction, followed by reverse transcription. Relative RNA levels were obtained, and quantitative polymerase chain reaction (qPCR) analysis was conducted to assess the efficiency of LINC00857 expression. The administration of a low dose of OXA promoted the migratory, invasive, and angiogenic capabilities of HSC-3 cells, while also regulating EMT-associated molecular markers to facilitate the process of EMT. The inhibitory impact on OSCC proliferation was enhanced by the synergistic effect of apigenin and OXA. Furthermore, the tumor-promoting effects induced by low-dose OXA were notably suppressed through LINC00857. Evidence from this study indicates that apigenin can effectively suppress the metastasis of OSCC cancer cells induced by low-dose OXA through inhibiting the level of LINC00857, suggesting a promising therapeutic strategy.

Differential effects of coverslip-induced hypoxia and cobalt chloride mimetic hypoxia on cellular stress, metabolism, and nuclear structure

Hypoxia has profound effects on cell physiology, both in normal or pathological settings like cancer. In this study, we asked whether a variant of coverslip-induced hypoxia that recapitulates the conditions found in the tumor microenvironment would elicit similar cellular responses compared to the well established model of cobalt chloride-induced hypoxia. Comparable levels of nuclear HIF-1α were observed after 24 h of coverslip-induced hypoxia or cobalt chloride treatment in CAL-27 oral squamous carcinoma cells. However, cellular stress levels assessed by reactive oxygen species production and lipid droplet accumulation were markedly increased in coverslip-induced hypoxia compared to cobalt chloride treatment. Conversely, mitochondrial ATP production sharply decreased after coverslip-induced hypoxia but was preserved in the presence of cobalt chloride. Coverslip-induced hypoxia also had profound effects in nuclear organization, assessed by changes in nuclear dry mass distribution, whereas these effects were much less marked after cobalt chloride treatment. Taken together, our results show that coverslip-induced hypoxia effects on cell physiology and structure are more pronounced than mimetic hypoxia induced by cobalt chloride treatment. Considering also the simplicity of coverslip-induced hypoxia, our results therefore underscore the usefulness of this method to recapitulate in vitro the effects of hypoxic microenvironments encountered by cells in vivo.