Oral Cancer Cells Research Articles

Eco-friendly synthesis of betanin-conjugated zinc oxide nanoparticles: antimicrobial efficacy and apoptotic pathway activation in oral cancer cells.

Phytochemical-based synthesis of nanoparticles (NPs) is an eco-friendly approach with various biomedical applications. Betanin, a natural pigment in beetroot, has antioxidant, anti-inflammatory, and antimicrobial properties. When conjugated with zinc oxide nanoparticles (ZnO NPs), these properties are enhanced. This study aimed to synthesize betanin-ZnO nanoparticles (BE-ZnO-NPs) and evaluate their biological potential. BE-ZnO-NPs were synthesized and characterized using UV-Visible spectroscopy, FTIR, FE-SEM, HR-TEM, EDX, XRD, DLS, and zeta potential analysis. In silico studies assessed interactions with oral pathogen proteins, and antibacterial activity was tested against Enterococcus faecalis, Candida albicans, Staphylococcus aureus and Streptococcus mutans. Antioxidant potential and cytotoxicity on KB cells were evaluated through scavenging assays, MTT assay, and qRT-PCR. Betanin synthesized ZnO NPs UV-Vis results showed surface plasmon resonance at 388 nm, and FTIR confirmed betanin role as a capping agent. FE-SEM and TEM revealed particles of 37 nm. EDX confirmed zinc content, and XRD showed a hexagonal structure. Zeta potential was -3.3 mV, and DLS indicated a size of 38.73 nm. In silico analysis showed strong binding to E. faecalis (-8.0 Kcal/mol). BE-ZnO-NPs demonstrated antibacterial activity at 100 µg/mL, with inhibition zones of 18 ± 0.14 mm for E. faecalis and 14 ± 0.18 mm for S. mutans. In contrast, BE demonstrated antibacterial activity at 100 µg/mL, with zone of inhibition of 10.6 ± 0.14 mm for E. faecalisand 11.4 ± 0.18 mm for S. mutans.Antioxidant assays revealed dose-dependent scavenging activity. Cytotoxicity showed an IC50 of 24.29 µg/mL, with qRT-PCR indicating apoptosis through the BCL2/BAX/P53 pathway. BE-ZnO-NPs exhibited significant antibacterial and antioxidant activities and demonstrated the ability to induce apoptosis in oral cancer cells via the BCL-2/BAX/P53 signalling pathway. These findings highlight the potential of BE-ZnO-NPs as promising antimicrobial agents for tooth infections and as therapeutic agents for oral tumour treatment.

Upregulation of ENAH by a PI3K/AKT/β-catenin cascade promotes oral cancer cell migration and growth via an ITGB5/Src axis

BackgroundOral cancer accounts for 2% of cancer-related deaths globally, with over 90% of cases being oral cavity squamous cell carcinomas (OSCCs). Approximately 50% of patients with OSCC succumb to the disease within 5 years, primarily due to the advanced stage at which it is typically diagnosed. This underscores an urgent need to identify proteins related to OSCC progression to develop effective diagnostic and therapeutic strategies.MethodsTo identify OSCC progression-related proteins, we conducted integrated proteome and transcriptome analyses on cancer tissues from patients and patient-derived xenograft (PDX) model mice. We investigated the role of protein-enabled homolog (ENAH), identified as an OSCC progression-associated protein, through proliferation, transwell migration, and invasion assays in OSCC cells. The mechanisms underlying ENAH-mediated functions were elucidated using gene knockdown and ectopic expression techniques in OSCC cells.ResultsENAH was identified as a candidate associated with OSCC progression based on integrated analyses, which showed increased ENAH levels in primary OSCC tissues compared with adjacent noncancerous counterparts, and sustained overexpression in the cancer tissues of PDX models. We confirmed that level of ENAH is increased in OSCC tissues and that its elevated expression correlates with poorer survival rates in patients with OSCC. Furthermore, the upregulation of ENAH in OSCC cells results from the activation of the GSK3β/β-catenin axis by the EGFR/PI3K/AKT cascade. ENAH expression enhances cell proliferation and mobility by upregulating integrin β5 in oral cancer cells.ConclusionsThe upregulation of ENAH through a PI3K/AKT/β-catenin signaling cascade enhances oral cancer cell migration and growth via the ITGB5/Src axis. These findings offer a new interpretation of the ENAH function in the OSCC progression and provide crucial information for developing new OSCC treatment strategies.

FNDC5 affects invasion and migration of oral cancer by inhibiting PI3K/Akt/Snail signaling pathway

This study first investigated how FNDC5 affected the development of oral cancer and revealed the role of FNDC5 in the migration and invasion of oral cancer. The present work evaluated differential FNDC5 expression within oral cancer samples versus matched non-carcinoma samples based on GEO database analysis and immunohistochemistry. We then generated oral cancer cell lines with FNDC5 overexpression and knockdown to determine the role of altered FNDC5 expression in the migration and invasion of oral cancer. PI3K inhibitor was used for investigating the possible mechanism underlying FNDC5 during EMT of oral cancer. Finally, these in-vitro results were validated using the lung metastatic nude mouse model. According to our results, FNDC5 level markedly decreased within oral cancer compared with adjacent samples and FNDC5 overexpression inhibited migration, invasion as well as EMT of oral cancer, while FNDC5 knockdown promoted oral cancer cell EMT. In addition, PI3K inhibitors blocked the induction of oral cancer cells EMT by FNDC5 knockdown. In vivo experiments further demonstrated the above results. This work is the first to illustrate the impact of FNDC5 on inhibiting migration and invasion of oral cancer, and our results suggest that FNDC5 affects EMT of oral cancer via the inhibition of PI3K/Akt/Snail pathway.

SIGMAR1 Knockdown Enhances Oral Cancer Cell Chemosensitivity to Cisplatin via Decreased PD-L1 Expression

Emerging evidence suggests that aberrant expression levels of Sigma1 (SIGMAR1, also known as sigma-1 receptor) have been implicated in the progression of various diseases, including cancer. However, its significance in oral cancer (OC) has not been thoroughly explored. To advance in this field, the present study aimed to investigate the impact of SIGMAR1 knockdown in oral cancer cells. To do so, we included in this study our cohort of human OC samples and OC cell lines, which were utilized for experimental verification through several in vitro assays. Our findings revealed that SIGMAR1 overexpression was associated with poor survival rates and positively correlated with PD-L1 overexpression in human oral cancer samples. Furthermore, SIGMAR1 inhibition led to a decrease in PD-L1 expression and sensitized oral cancer cells to cisplatin treatment by enhancing apoptosis. These results suggest that SIGMAR1 knockdown may present a promising strategy worthy of further exploration in the management of oral cancer.

Shikonin Stimulates Mitochondria-Mediated Apoptosis by Enhancing Intracellular Reactive Oxygen Species Production and DNA Damage in Oral Cancer Cells.

Phytotherapy has rendered a new insight towards the treatment of various cancers, including oral cancer with fewer side effects, over the traditional chemotherapeutic drugs to overcome chemoresistance. Shikonin (Shk) is a natural biologically active alkaloid found in the Lithospermum erythrorhizon plant's root. It has potent cytotoxic activities against various cancers. Our study revealed the release time and anticancer potential of Shk on the SCC9 and H357 oral cancer cell lines. We investigated the antiproliferative, antimigratory, cell cycle arresting and apoptosis promoting activity of Shk in oral cancer cells by performing MTT and morphological assay, colony, and tumor sphere formation assay, AO/EtBr and DAPI staining, Annexin V-FITC/PI staining, assay for reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) measurement, comet assay, qRT-PCR, and western blot analysis. We also checked the interaction of DNA and Shk by docking and CD spectroscopy and EtBr displacement assay. As a result, we found that Shk reduced the viability, proliferation, and tumorigenicity of SCC9 and H357 cells in a time and concentration-dependent manner. We obtained half-maximal inhibitory concentration (IC50) at 0.5 µM for SCC9 and 1.25 µM for H357. It promotes apoptosis via overexpressing proapoptotic Bax and caspase 3 via enhancing ROS that leads to MMP depletion and DNA damage and arrests cells at the G2/M & G2/S phase. The antimigratory activity of Shk was performed by analyzing the expression of markers of epithelial-mesenchymal transition like E-cadherin, ZO-1, N-cadherin, and vimentin. These overall results recommended that Shk shows potent anticancer activity against oral cancer cell lines in both in vitro and ex vivo conditions. So, it could be an excellent agent for the treatment of oral cancer.

Prolonged glutamine starvation reactivates mTOR to inhibit autophagy and initiate autophagic lysosome reformation to maintain cell viability.

Autophagy, a cellular recycling mechanism, utilizes lysosomes for cellular degradation. Prolonged autophagy reduces the pool of functional lysosomes in the cell. However, lysosomal homeostasis is maintained through the regeneration of functional lysosomes during the terminal stage of autophagy, i.e. Autophagic lysosome reformation (ALR). Through confocal microscopy during glutamine starvation, we unravel the regeneration of tubules from autolysosomes by undertaking significant membrane remodeling, which majorly depends on mTOR reactivation, RAB7 dissociation, phosphatidyl inositol 3 phosphate (PI3P) dependent dynamin 2 and clathrin recruitment. In glutamine-starved cells, we found mTOR is the central modulator in regulating ALR initiation, and its pharmacological inhibition with rapamycin leads to a decrease in lysosomal tubulation. Moreover, RAB7 and Clathrin are essential for tubule elongation and it showed that siRNA targeting RAB7 and Clathrin restricts tubule initiation under glutamine starvation. In this setting, we examined the physiological relevance of ALR during prolonged glutamine deprivation and found that genetic and pharmacological inhibition of critical proteins involved in ALR promotes cell death in oral cancer cells, establishing ALR is essential for maintaining cell survival during stress.

Synergistic Action of Rutin-Coated Zinc Oxide Nanoparticles: Targeting Biofilm Formation Receptors of Dental Pathogens and Modulating Apoptosis Genes for Enhanced Oral Anticancer Activity.

Oral diseases are often associated with bacterial and fungal pathogens such as Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Candida albicans. This research explored a novel approach to addressing these pathogens by synthesizing zinc oxide nanoparticles (ZnO NPs) coated with rutin (RT), a plant-derived compound. The synthesized ZnO-RT NPs were comprehensively characterized using UV-Vis spectrophotometer, SEM, and EDAX techniques to confirm their structural composition. The antioxidant potential was assessed through free radical scavenging assays. Additionally, the antimicrobial activity of ZnO-RT NPs was evaluated using a zone of inhibition assay against oral pathogens. Molecular docking studies with the Autodock tool were performed to elucidate the interactions between RT and the receptors of oral pathogens. The findings demonstrated that ZnO-RT NPs exhibited robust free radical scavenging activity. Furthermore, they showed significant antimicrobial activity with a minimal inhibitory concentration of 40 μg/mL against oral pathogens. ZnO-RT NPs also displayed dose-dependent anticancer effects on human oral cancer cells at concentrations of 10, 20, 40, and 80 μg/mL. Mechanistic insights into the anticancer activity on KB cells revealed the upregulation of apoptotic genes. This study underscores the promising potential of ZnO-RT NPs for dental applications due to their strong antioxidant, anticancer, and antimicrobial properties. These nanoparticles offer a hopeful prospect for addressing oral pathogen challenges and enhancing overall oral health.

Jing-Si Herbal Tea attenuates oral cancer cell viability, migration, and invasion by regulating epithelial-to-mesenchymal transition and reactive oxygen species accumulation

Background/purposeOral cancer is the sixth most common cancer worldwide and can be life-threatening if not diagnosed and treated in its early stages. Jing-Si Herbal Tea (JSHT), containing eight traditional Chinese medicine-based herbs, is known to suppress the malignancy, growth, and metastasis of several tumor cells, including breast, lung, and colon cancer cells. However, the pharmacological effect of JSHT on oral cancer progression is still unclear. Materials and methodsIn this study, we evaluated the potential of JSHT to arrest the development of oral cancer via induction of cell death by reactive oxygen species (ROS) accumulation and inhibition of migration, invasion, and epithelial-to-mesenchymal transition (EMT). For this purpose, we employed the human tongue squamous cell carcinoma SAS cell line, which we treated with different JSHT concentrations for 24 h, and assessed cell viability, migration, and wound healing capabilities, together with western blotting for measuring expression levels of EMT markers. ResultsSurvival, migration/invasion ability, EMT, and ROS production in the SAS human tongue squamous carcinoma and FaDu human pharynx squamous cell carcinoma cell line were decreased by JSHT treatment via Lon protease-independent mechanisms. ConclusionThis study demonstrates that JSHT could be regarded as a candidate new supplement to existing anticancer therapies and an alternative, orally administered healthcare product for treating oral squamous cell carcinoma.

LINC00342 regulates the PI3K-AKT signaling pathway via the miR-149-5p/FGF11 axis and affects the progression of oral cancer

BackgroundA large number of long non-coding RNAs (lncRNAs) have been implicated in the progression of oral cancer (OC). This study aimed to investigate the role of a novel lncRNA, LINC00342, in OC and elucidate its molecular mechanism.MethodsDifferential expression of lncRNA/miRNA/mRNA was analyzed using the Gene Expression Omnibus database and validated with RT-qPCR. Additionally, the expression levels of these molecules in OC cells and their effects on cell viability and cell cycle were assessed using the Cell Counting Kit-8 and flow cytometry. RNA bindings was analyzed by dual luciferase, and Western blot was used to detect the activation of relevant pathways.ResultsThis study showed that, in contrast to miR-149-5p, the expression of LINC00342 and fibroblast growth factor 11 (FGF11) were upregulated in OC cells (LINC00342: 10.00 ± 1.06 (FaDu) and 3.55 ± 0.25 (CAL-27) vs 1.00 ± 0.07 (HOECs), P < 0.05; FGF11: 7.31 ± 0.33 (FaDu) and 3.43 ± 0.08 (CAL-27) vs 1.00 ± 0.10 (HOECs), P < 0.05). Dual-luciferase assays confirmed that LINC00342 bind to miR-149-5p in a direct targeting manner. Furthermore, inhibition of LINC00342 expression resulted in decreased proliferation rate (FaDu: 136.22 ± 22.10% vs 59.36 ± 8.98% (control), P < 0.05; CAL-27: 131.40 ± 11.58% vs 49.83 ± 11.19 (control), P < 0.05) and migration ability of OC cells, cell cycle arrest in G1 phase, and inhibition of PI3K-AKT signaling. Inhibition of miR-149-5p or overexpression of FGF11 reversed the effects of si-LINC00342.ConclusionsLINC00342 promotes PI3K-AKT signaling by activating FGF11 through adsorption of miR-149-5p, thereby regulating the progression of OC.

ZNF671 Silencing Affects Signaling Pathways in Head and Neck Cancer via Activation of Oncogenic Non-Coding RNAs

Background: Novel ZNF genes, such as ZNF671, that are located on chromosome 19q13 are known to be hypermethylated at a high frequency in HNSCC as well as in other epithelial solid tumors. Their function is largely unknown. Results: Here, we show that ZNF671 is epigenetically silenced in HNSCC primary tumors compared to matched adjacent normal tissue. Moreover, low expression of ZNF671 is significantly associated with decreased survival in HNSCC patients. Over-expression of ZNF671 in UM-SCC-1 oral cancer cells resulted in a significant reduction in tumor cell mobility and invasion compared to the empty-vector control cells. Transcriptomic analysis showed that ZNF671 re-expression resulted in a significant decrease in the expression of a major oncogenic long non-coding RNA LINC00665. Conclusions: Together, these results suggest that epigenetic silencing of ZNF671 may activate multiple oncogenic signaling pathways via the resulting up-regulation of LINC00665.

Construction of oral cancer microenvironment model using 3D culture technology and search for new therapeutic targets

There remains much to be discovered and understood about the subtypes of cancer associated-fibroblasts (CAFs) in oral cancer. At the Faculty of Dentistry, Niigata University in Japan, Dr Kenta Haga is investigating the tumour microenvironment and CAFs. To do this, he and his team are using 3D culture technology in their studies as 3D culture models are considered to be more useful and more faithful to the biological characteristics and drug resistance of cancer than 2D cultures. This is because cells are never in 2D in the human body; they are all placed in a 3D structural environment. In their latest study, the researchers utilised their experimental model to recreate the cancer microenvironment and evaluate the proliferation and invasion of cancer cells over time. They have incorporated CAFs into a collagen gel, seeded oral cancer cells and established the basic technology for a 3D culture model with a two-layered structure that has a tumour layer and an interstitial layer to mimic squamous cell carcinoma. The team has been able to investigate the interaction of CAFs with oral cancer cells by in vitro, in vivo and in human oral cancer specimens. In order to understand the complex tumour microenvironment they are seeking to analyse the effects of CAFs on the invasive and proliferative potential for cancer cells. If they can elucidate the intercellular network in the tumour microenvironment, this will lead to novel treatment strategies for cancer. Haga and the team have already demonstrated that the TGF-β/SOX9 pathway plays an important role in CAFs promoting epithelial mesenchymal transition (EMT) in oral cancer.

Natural compounds targeting miRNAs: a novel approach in oral cancer therapy.

Oral cancer (OC) is a significant global health issue, with high rates of both mortality and morbidity. Conventional treatments, including surgery, radiation, and chemotherapy, are commonly used, but they often come with serious side effects and may not fully eliminate cancer cells, resulting in recurrence and resistance to treatment. In recent years, natural products derived from plants and other biological sources have gained attention for their potential anticancer properties. These compounds offer advantages such as lower toxicity compared to traditional chemotherapy. Notable natural compounds like quercetin, berberine, curcumin, andrographolide, nimbolide, ovatodiolide, and cucurbitacin B have demonstrated effectiveness in inhibiting OC cell growth by targeting various signaling pathways involved in cancer progression. Recent breakthroughs in molecular biology have highlighted the crucial role of microRNAs (miRNAs) in the development of OC. Targeting dysregulated miRNAs with natural products offers a promising strategy for treating the disease. Natural compounds exert anticancer effects by influencing both altered cellular signaling pathways and miRNA expression profiles. This study aims to explore the role of miRNAs as potential molecular targets in OC and to investigate how natural products may regulate these miRNAs. Additionally, this review will shed light on the therapeutic potential of phytochemicals in modulating miRNA expression and their significance in OC treatment.

A Dual Approach by Nanostructured α-Mangostin-Copper Oxide Complexes Against Dental Pathogen Biofilms and Oral Cancer via Apoptosis Gene Modulation.

The development of effective treatments for dental pathogens and oral cancer remains a significant challenge. Copper oxide nanoparticles (CuO NPs) are recognized for their strong antimicrobial properties, attributed to the synthesis of oxygen-dependent radicals. α-Mangostin (MG), a natural xanthone from mangosteen fruit, is well-known for its antioxidant, antimicrobial, and anticancer potential. Antioxidant activity was assessed using superoxide anion and hydroxyl radical anion. The anticancer potential was evaluated by examining apoptosis induction in oral cancer cell lines, focusing on the expression of key apoptotic markers such as Caspase-3, Caspase-8, and FasL. Molecular docking simulations were performed to understand the interaction between MG and biofilm receptors. The CuO-MG NPs evidenced significant antimicrobial efficacy against all tested oral pathogens, with enhanced efficacy attributed to the combined effects of CuO-induced oxidative stress and the antimicrobial properties of MG. Molecular docking studies revealed strong binding affinities of MG to key biofilm receptors, disrupting pathogen adhesion and biofilm formation. CuO-MG NPs demonstrate synergistic antimicrobial, antioxidant, and anticancer properties, offering a potential approach for the management of oral infections and oral cancer. Further preclinical and clinical studies are recommended to ensure their safety and stability in medical applications.

Anticancer effect of surface functionalized nano titanium dioxide with 5‐fluorouracil on oral cancer cell line—An in vitro study

Anticancer effect of surface functionalized nano titanium dioxide with 5‐fluorouracil on oral cancer cell line—An in vitro study

Anti-Oxidant and Anti-Cancerous Properties of Pyrus pashia (Buch. -Ham.Ex D.Don) Against KB-3-1 Cancer Cell Lines In Vitro

Background: Oral cancer is the fastest-growing cancer in men. Many medicinal approaches are tried step-wise for cancers. Homeopathy and Ayurveda are contributing much to cure cancers without side effects. Plants having antioxidant properties are now being utilized with different solvents to extract different chemical compounds to cure cancer. Objective: The current study aimed to examine the anti-cancer and antioxidant properties of acetone extract of Pyrus pashia (PP-AE) fruit against KB-3-1 cancer cell lines. Materials and Methods: The extract's total phenolic content was determined using a folin-ciocalteu reagent. The DPPH, ABTS, and H2O2 assay were used to measure the free radical scavenging activity of the PP-AE. The MTT assay was used to evaluate the cytotoxic efficacy of the PP-AE against KB-3-1 cancer cell lines at various concentrations. Results: Based on the observations, the total phenolic content was present in the PP-AE of fruit and all free radical scavenging assays have shown remarkable IC50 values. Conclusion: According to the current study, acetone extract of Pyrus pashia fruit significantly possesses antioxidant and anti-cancer properties against oral (KB-3-1) cancer cell lines. This effect may be used in the future to analyze particular chemical compounds in extract, capable of minimizing the growth of oral cancer cells.

In Vitro Anticancer Potential of Eugenol on Oral Cancer Cell Lines: A Systematic Review.

Oral cancer is one of the most common types of cancer and has become a global health concern. Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer worldwide. Eugenol, an aromatic phenolic compound, exhibits various pharmacological activities, including anticancer effects. Several studies have reported the anticancer activity of eugenol against OSCC via different pathways. However, no current review has discussed the extent of eugenol anticancer research on oral cancer cell lines using in vitro studies. This systematic review aimed to discuss the anticancer potential of eugenol against oral cancer cell lines in vitro. Articles were selected from PubMed, ScienceDirect, SpringerLink and EBSCOhost databases based on specified inclusion and exclusion criteria. Additional articles were identified through manual hand searching. The selection process followed PRISMA guidelines. A risk-of-bias assessment was performed to evaluate the reliability and relevance of the in vitro studies. Thirteen articles with high-quality results were assessed and analysed for further investigation. These studies investigated the ability of eugenol to induce cell death through apoptotic and non-apoptotic pathways, inhibit cell proliferation and affect oxidative stress, contributing to cell death in several oral cancer cell lines. Therefore, eugenol is a potential anticancer agent for OSCC, as it exhibited anticancer activity in oral cancer cell lines in vitro studies.

Comparative evaluation of anticancer potential of Spilanthes paniculata leaf and flower essential oil using annexin V and orosphere formation in oral cancer cell line.

Spilanthes paniculata, a member of the Asteraceae family, is predominantly used as a traditional remedy in addressing oral ailments, particularly gum infections and sore throat. The flowers are chewed to alleviate toothache immediately. This study evaluated a comparison between the essential oils of leaf and flower derived from Spilanthes paniculata targeting the SCC9 oral cell lines using in vitro and in silico approaches. The anticancer activity was performed through an MTT assay, apoptosis assays using annexin V and orospheres formation assays. Molecular docking was performed between five selected phytocompounds against the p53 protein by using AutoDock 4.2.6 software. The results confirmed that the flower essential oil significantly reduced the cell viability in a dose-dependent manner, with an IC50 value of 113.95µg/mL. The apoptosis assays showed that the flower essential oil was approximately 2.5 times more effective in inducing early apoptosis at 50µg/mL compared to the essential oil of the leaf. The orosphere formation assays further confirmed the anticancer potential of the flower essential oil. Spathulenol exhibited strong hydrogen bonding with the p53 protein. The ADMET prediction tools were used to predict the in silico pharmacokinetics and drug-like properties of the phytoconstituents. The results suggested that Spathulenol and Nerolidol have high gastrointestinal absorption (GIA), with estimated solubility (ESOL) values of -3.17 and -3.22, respectively, falling within the optimal range. These findings suggest that the flower's essential oil efficiently prevented the proliferation of oral cancer and observed a notable degree of cell death, inducing apoptosis and suggesting its significant antiproliferative activity against cancerous cell line which could be explored further for therapeutic applications.

Roles of ZEB1 and ZEB2 in E-cadherin expression and cell aggressiveness in head and neck cancer.

Zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in cancer cell differentiation and metastasis, and has been well studied in the field of cancer cell biology. ZEB2 has a highly similar conformation to ZEB1, but its role in head and neck squamous cell carcinoma (HNSCC) cells is not fully understood. Here, we separately overexpressed ZEB1 and ZEB2 in C57BL/6 mouse oral cancer (MOC) cells and investigated their cellular characteristics, including E-cadherin levels, motile properties, chemoresistance, and metastatic ability in immunocompetent mice. Both ZEB1 and ZEB2 overexpression reduced epithelial traits and converted cells to an aggressive phenotype. Surprisingly, ZEB1 overexpression increased the endogenous level of ZEB2 in MOC cells, and vice versa. The molecular mechanisms underlying these findings remain unclear. However, the in vitro anchorage-independent growth of MOC cells overexpressing ZEB2 was considerably greater than that of MOC cells overexpressing ZEB1. These findings suggest that ZEB2, like ZEB1, has the ability to induce the differentiation of cancer cells into those with highly aggressive traits.

PAR2 on oral cancer cells and nociceptors contributes to oral cancer pain that can be relieved by nanoparticle-encapsulated AZ3451

Oral cancer is notoriously painful. Activation of protease-activated receptor 2 (PAR2, encoded by F2RL1) by proteases in the cancer microenvironment is implicated in oral cancer pain. PAR2 is a G protein-coupled receptor (GPCR) expressed on neurons and cells in the cancer microenvironment. Sustained signaling of PAR2 from endosomes of neurons mediates sensitization and nociception. We focused on the differential contribution of PAR2 on oral cancer cells and neurons to oral cancer pain and whether encapsulation of a PAR2 inhibitor, AZ3451 in nanoparticles (NP) more effectively reverses PAR2 activation. We report that F2RL1 was overexpressed in human oral cancers and cancer cell lines. Deletion of F2RL1 on cancer cells reduced cancer-associated mechanical allodynia. A third-generation polyamidoamine dendrimer, functionalized with cholesterol was self-assembled into NPs encapsulating AZ3451. NP encapsulated AZ3451 (PAMAM-Chol-AZ NPs) more effectively reversed activation of PAR2 at the plasma membrane and early endosomes than free drug. The PAMAM-Chol-AZ NPs showed greater efficacy in reversing nociception than free drug, with respect to both level and duration, in three preclinical mouse models of oral cancer pain. The antinociceptive efficacy was confirmed with an operant orofacial assay. Genetic deletion of F2RL1 on cancer cells or F2rl1 on neurons each partially reversed mechanical cancer allodynia. The remaining nociception could be effectively reversed by PAMAM-Chol-AZ NPs. These findings suggest that PAR2 on oral cancer cells and neurons contribute to oral cancer nociception and NPs loaded with a PAR2 antagonist provide increased antinociception and improved oral function compared to free drug.

Investigating the Anticancer Potential of Biochanin A in KB Oral Cancer Cells Through the NFκB Pathway.

Squamous cell carcinoma (SCC) is a malignancy primarily affecting squamous cells. Its development is linked to multiple risk factors, such as alcohol and tobacco consumption, human papillomavirus (HPV) infection, and Epstein-Barr Virus (EBV) infection. Biochanin A (BCA), a phytoestrogen extracted from red clover, has been extensively researched for its therapeutic properties. It spans antioxidant activity, anti-inflammatory effects, neuroprotection, cardioprotection, and anticancer potential in different bodily systems. However, its impact on oral cancer remains unexplored. Therefore, this investigation aims to assess the potential anticancer effects of BCA, specifically on KB oral cancer cells. This study utilized KB cells to evaluate the impact of BCA on various cellular parameters, including cell viability, apoptosis, intracellular ROS production, mitochondrial membrane potential, and cell migration. BCA treatment induced several notable effects on KB cells, including reduced cell viability, altered morphology suggestive of apoptosis, heightened oxidative stress, and alterations in mitochondrial membrane potential. Moreover, BCA treatment demonstrated an inhibitory effect on cell migration. The study further investigated the impact of BCA on antioxidant enzyme activities and lipid peroxidation, revealing decreased antioxidant enzyme activities and increased lipid peroxidation across different BCA concentrations (IC50 and IC90). Immunocytochemistry and qRT-PCR analyses unveiled that BCA treatment at varying doses (IC50 and IC90) downregulated the expression of nuclear factor-κB (NF-κB) subunits p50 and p65, pivotal players in cancer progression. In summary, this study sheds light on the promising potential of BCA as an anticancer therapeutic agent for treating oral cancer. Its demonstrated ability to induce apoptosis, perturb cellular functions, and modulate gene expression within cancer cells underscores its significance. Nonetheless, further research, particularly following animal studies, is imperative to comprehensively grasp the breadth of BCA's effects and its viability for clinical applications.