Squamous Carcinoma Cell Lines Research Articles

Increased cell killing effect in neutron capture enhanced proton beam therapy

AbstractThermal neutrons generated in the body during proton beam therapy (PBT) can be used to cause boron neutron capture reactions and have recently been proposed as neutron capture enhanced PBT (NCEPBT). However, the cell killing effect of NCEPBT remains underexplored. Here, we show an increase in the cell killing effect of NCEPBT. Using Monte Carlo simulations, we showed that neutrons generated by proton beam irradiation are uniformly spread on tissue culture plates. Human salivary gland tumor cell line (HSG), human osteosarcoma cell line (MG63), human tongue squamous cell carcinoma cell line (SAS), and human malignant melanoma cell line (G-361) were irradiated with X-rays, proton beams, and proton beams with 10B-enriched boronophenylalanine (boron concentration of 20 and 80 ppm). The relative biological effectiveness (RBE) values of proton beams alone, proton beams with 20 ppm boron, and proton beams with 80 ppm boron for HSG, MG63, SAS, and G-361 were 1.02, 1.07, and 1.23; 1.01, 1.08, and 1.44; 1.05, 1.09, and 1.46; and 1.04, 1.13, and 1.63, respectively. NCEPBT with high boron concentration showed high RBE and a high sensitizing effect. Our results confirm an increase in the cell killing effect of NCEPBT, should aid in its clinical use, and warrant its further investigation.

Abstract B015: Targeting CX3CL1 transforms a cold tumor microenvironment into a hot one by enhancing T cells and DCs locally and systemically

Abstract Intratumoral heterogeneity (ITH) is associated with immunotherapy failure and a weaker anti- tumor immune response. Using a series of carcinogen-induced tumor (CIT) squamous cell skin carcinoma cell lines, our lab has sought to identify tumor-intrinsic factors—particularly chemokines and cytokines—which can have a “dominant negative” effect on the immune microenvironment when present within a heterogeneous tumor. We identified CX3CL1 as a one such critical mediator of a cold (T cell low) immune microenvironment and found that tumors containing as few as 10% CX3CL1high tumor cells exhibit a diminished T cell response compared to tumors which lack CX3CL1high tumor cells. We predicted that targeting CX3CL1 could therefore transform a cold tumor microenvironment (TME) into an inflammatory hot (T cell high) TME. Supporting this, we found that CRISPR-Cas9-mediated deletion of CX3CL1 in a tumor cell line that typically gives rise to cold tumors led to higher T cell infiltration and fewer immunosuppressive macrophages in the TME of CX3CL1-/- tumors. Building on this, we further explored T cell populations in the TME and found that CX3CL1-/- tumors had significantly increased activation and decreased exhaustion markers on T cells. Flow cytometry analysis showed higher expression of CD44 on effector CD4 T cells and an increase in the number of activated CD44+ PD1low CD4 T cells. By contrast, the frequency of CD4 T cells which were PD1High TIM3+ and PD1High TIM3+ TIGIT+ which represent a likely exhausted effector CD4 population was lower in CX3CL1-/- tumors than in counterpart control tumors. An interrogation of DC subsets in the TME further revealed a higher number of cDC1 and cDC2 populations in CX3CL1−/− tumors. To determine the effect of tumor-produced CX3CL1 on immune activity in lymphoid organs, we investigated T cell and DC markers in the spleen and tumor-draining lymph nodes during early tumor development. Spleens harvested 10 days after tumor injection showed higher infiltration of cDC1 CCR7+ and cDC2 CCR7+ mature DCs in CX3CL1-/- tumor-bearing mice. Thus, in the absence of tumor-produced CX3CL1, both cDC1 and cDC2 dendritic cell subsets attain more mature phenotypes in both the TME and the spleen. At the same time point, tumor-draining lymph nodes also exhibited a shift in immune cell composition characterized by an increased frequency of T cells, particularly CD4+ T cells, and a decreased frequency of B cells. Moreover, the percentage of PD1+ CD8 cells was also higher, indicating better priming and activation of CD8 T cells via DCs in tumor-draining lymph nodes. These findings indicate that tumor-produced CX3CL1 drives a cold immune microenvironment through both tumor-localized and systemic effects. These studies suggest therapeutically targeting CX3CL1 particularly in tumors where tumor cells produce high levels of CX3CL1 holds promise to transform a cold TME into a hot immune inflammatory TME and potentiate better anti-tumor immunity. Citation Format: Piyush Chaudhary, Savannah Hughes, Joshua Tay, Robert Letchworth, Miho Tanaka, Melissa Reeves. Targeting CX3CL1 transforms a cold tumor microenvironment into a hot one by enhancing T cells and DCs locally and systemically [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B015.

Melanoma Cells from Different Patients Differ in Their Sensitivity to Alpha Radiation-Mediated Killing, Sensitivity Which Correlates with Cell Nuclei Area and Double Strand Breaks

Background/Objective: In this study, for the first time, we examined and compared the sensitivity of four patient-derived cutaneous melanoma cell lines to alpha radiation in vitro and analyzed it in view of cell nucleus area and the formation of double-strand breaks (DSB). Melanoma cells sensitivity to alpha radiation was compared to photon radiation effects. Furthermore, we compared the sensitivity of the melanoma cells to squamous cell carcinoma. Methods: Human melanoma cell lines YDFR.C, DP.C, M12.C, and M16.C, and the squamous cell carcinoma cell line, CAL 27, were irradiated in vitro using Americium-241 as alpha-particle source. Cells were irradiated with doses of 0 to 2.8 gray (Gy). Cell viability, DNA DSB, and nuclear size were measured. Results: 1. Alpha radiation caused death and proliferation arrest of all four melanoma cell lines, but inter-tumor heterogeneity was observed. 2. The most sensitive cell line (DP.C) had a significantly larger nucleus area (408 µm2) and the highest mean number of DSB per cell (9.61) compared to more resistant cells. 3. The most resistant cell, M16.C, had a much lower nucleus area (236.99 µm2) and DSB per cell (6.9). 4. Alpha radiation was more lethal than photon radiation for all melanoma cells. 5. The SCC cell, CAL 27, was more sensitive to alpha radiation than all melanoma cells but had a similar number of DSB (6.67) and nucleus size (175.49 µm2) as the more resistant cells. 6. The cytotoxic effect of alpha radiation was not affected by proliferation arrest after serum starvation. 7. Killing of cells by alpha radiation was marginally elevated by ATR or topoisomerase 1 inhibition. Conclusions: This study demonstrates that various human melanoma cells can be killed by alpha radiation but exhibit variance in sensitivity to alpha radiation. Alpha radiation applied using the Intra-tumoral Diffusing alpha-emitters Radiation Therapy (Alpha DaRT) methodology may serve as an efficient treatment for human melanoma.

KS-cSCC-1 and KS-cSCC-2: two novel cutaneous squamous cell carcinoma cell lines established from Japanese patients

KS-cSCC-1 and KS-cSCC-2: two novel cutaneous squamous cell carcinoma cell lines established from Japanese patients

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.

Carboxymethyl chitosan-modified folate-targeted carbon nanotubes-baicalin complexes for cancer progression and metastasis

Achieving desirable clinical outcomes is difficult given the rising number of cases and mortality of oral squamous cell carcinoma. Consequently, developing an efficient drug delivery system for managing cancer progression and metastasis with relatively low toxicity has proven to be highly promising. Initially, carboxymethyl chitosan was covalently modified and partially substituted with folic acid, and subsequently encapsulated as a shell to deliver carboxylated multiwalled carbon nanotubes and their coupled baicalin to form carboxymethyl chitosan-modified folate-targeted carbon nanotubes-baicalein complexes. The impact on the normal cell line HOK and the oral squamous cell carcinoma cell line CAL27 was assessed using CCK8, live-dead cell assay, colony formation assay, flow cytometry, wound healing assay, and transwell migration and invasion assays. These analyses confirmed that the complexes induced apoptosis in cancer cells and reduced the migration and invasion of CAL27 cells. Additionally, the complexes demonstrated enhanced biosafety, significantly inhibited the growth of xenograft tumors and tissue metastasis, and altered the expression of proteins associated with epithelial-mesenchymal transition. The results mentioned above imply that the complexes may offer novel applications and serve as an effective strategy for preventing cancer spread and metastasis.

Impact of Hypoxia and the Levels of Transcription Factor HIF-1α and JMJD1A on Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cell Lines.

This study aimed to assess the impact of hypoxia on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC), focusing on the involvement of transcription factors hypoxia inducible factor 1 (HIF-1α) and Jumonji Domain-Containing Protein 1A (JMJD1A). FaDu and Cal33 cell lines were subjected to hypoxic and normoxic conditions. Cell proliferation was quantified electronically, while PCR and western blot analyses were used to measure mRNA and protein levels of HIF-1α, JMJD1A, and EMT markers. EMT was further characterized through immunofluorescence, migration, and invasion assays. Hypoxic conditions significantly reduced cell proliferation after 48 hours in both cell lines. HIF-1α mRNA levels increased initially during short-term hypoxia but declined thereafter, while JMJD1A mRNA levels showed a sustained increase with prolonged hypoxia. Western blot analysis revealed contrasting trends in protein levels. EMT marker expression varied markedly over time at both the mRNA and protein levels, suggesting EMT induction in hypoxia within 24 hours. Immunofluorescence, migration, and invasion assays supported these findings. The study provides evidence of hypoxia-induced EMT in HNSCC, although conflicting results suggest a complex interplay among molecular regulators involved in this process.

Glutamine and serum starvation alters the ATP production, oxidative stress, and abundance of mitochondrial RNAs in extracellular vesicles produced by cancer cells

Induction of autophagy represents an effective survival strategy for nutrient-deprived or stressed cancer cells. Autophagy contributes to the modulation of communication within the tumor microenvironment. Here, we conducted a study of the metabolic and signaling implications associated with autophagy induced by glutamine (Gln) and serum starvation and PI3K/mTOR inhibitor and autophagy inducer NVP-BEZ235 (BEZ) in the head and neck squamous cell carcinoma (HNSCC) cell line FaDu. We compared the effect of these different types of autophagy induction on ATP production, lipid peroxidation, mitophagy, RNA cargo of extracellular vesicles (EVs), and EVs-associated cytokine secretome of cancer cells. Both BEZ and starvation resulted in a decline in ATP production. Simultaneously, Gln starvation enhanced oxidative damage of cancer cells by lipid peroxidation. In starved cells, there was a discernible fragmentation of the mitochondrial network coupled with an increase in the presence of tumor susceptibility gene 101 (TSG101) on the mitochondrial membrane, indicative of the sorting of mitochondrial cargo into EVs. Consequently, the abundance of mitochondrial RNAs (mtRNAs) in EVs released by FaDu cells was enhanced. Notably, mtRNAs were also detectable in EVs isolated from the serum of both HNSCC patients and healthy controls. Starvation and BEZ reduced the production of EVs by cancer cells, yet the characteristic molecular profile of these EVs remained unchanged. We also found that alterations in the release of inflammatory cytokines constitute a principal response to autophagy induction. Importantly, the specific mechanism driving autophagy induction significantly influenced the composition of the EVs-associated cytokine secretome.

Oxymatrine inhibits migration and invasion of esophageal squamous cell carcinoma cell lines via the MEK1/ERK/β-catenin pathway

Esophageal, cancer is a prevalent malignant tumour of the digestive system in China, and esophageal squamous cell carcinoma (ESCC) accounts for 90 % of all esophageal cancer cases. Currently, the primary treatment involves surgical resection combined with postoperative radiotherapy. In this study, we used two ESCC cell lines to determine whether oxymatrine (OMT) inhibits ESCC, whether the mechanism involves the MEK1/ERK/β-catenin pathway, and how OMT modulates this pathway to affect the development of ESCC. The effects of OMT treatment were monitored with Cell Counting Kit-8 (CCK-8) assays as well as with clony formation, migration and invasion, wound healing, Hoechst 33258, and Western blot analyses. The relationship between OMT and the target was also evaluated by molecular docking and cell stability experiments. These findings suggest that ESCC development and metastasis may be inhibited by OMT and that OMT targets MEK1 through the ERK/β-catenin/EMT pathway to suppress ESCC cell migration and invasion. In addition, in vivo studies confirmed that OMT can inhibit the growth of ESCC cell lines in NOG mice without causing damage to other organs. In conclusion, in vitro experiments, revealed that OMT prevents the migration and invasiveness of ESCC cells by inhibiting the ERK/β-catenin/EMT pathway and thus targeting MAP2K1 (MEK1) in ESCC.

Optimization of the Treatment of Squamous Cell Carcinoma Cells by Combining Photodynamic Therapy with Cold Atmospheric Plasma

Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP–red light seems to be more efficacious than CAP-ALA–red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16INK4a, p21CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies.

Antibacterial profile and antiproliferative activities over human tumor cells of new silver(I) complexes containing two distinct trifluoromethyl uracil isomers

New silver(I) complexes of 5-(trifluoromethyl)uracil (5TFMU) and 6-(trifluoromethyl)uracil (6TFMU) isomers were synthesized, characterized, and evaluated as antibacterial and antiproliferative agents. Based on elemental and thermogravimetric analyses, the Ag-5TFMU and Ag-6TFMU species are formulated as AgC5H2F3N2O2 and Ag2C5HF3N2O2, respectively. Infrared and 13C solid-state nuclear magnetic resonance spectroscopies suggest coordination of the trifluoromethyluracil isomers to silver by both nitrogen and oxygen atoms. Confirmation of their structure and connectivity was achieved, in the absence of single crystals of suitable quality, by state-of-the-art structural powder diffraction methods. In Ag-5TFMU, the organic ligand is tridentate and two distinct metal coordination environments are found (linear AgN2 as well as C2v AgO4 geometries), whereas Ag-6TFMU contains a complex polymeric structure with tetradentate dianionic 6TFMU moieties and five distinct AgX2 (X = N, O) fragments, further stabilized by ancillary (longer) Ag…O contacts. These species presented modest activity over Gram-positive and Gram-negative bacterial strains, whereas Ag-6TFMU was active over a set of tumor cells, with the best activity over prostate (PC-3) and kidney cell lines and selectivity indices of 4.6 and 1.3, respectively. On the other hand, Ag-5TFMU was active over all considered tumor cells except MCF-7 (breast cancer). The best activity was found for PC-3 cells, but no selectivity was observed. The Ag-5TFMU and Ag-6TFMU species also reduced the proliferation of tongue squamous cell carcinoma cell lines SCC − 4 and SCC-15. Preliminary biophysical assays by circular dichroism suggest that the Ag-5TFMU complex interacts with DNA by intercalation, an effect not seen in Ag-6TFMU.

Anticancer effect of Artichoke and Fennel seeds extracts on oral squamous cell carcinoma cell line: In vitro study

Anticancer effect of Artichoke and Fennel seeds extracts on oral squamous cell carcinoma cell line: In vitro study

Oleanolic acid inhibits aldo-keto reductase family 1 member B10-induced cancer stemness and avoids cisplatin-based chemotherapy resistance via the Snail signaling pathway in oral squamous cell carcinoma cell lines

Background/purposeOral squamous cell carcinoma (OSCC) is a common malignancy often associated with poor prognosis due to chemoresistance. In this study, we investigated whether arecoline, a major alkaloid in betel nuts, can stimulate aldo-keto reductase family 1 member B10 (AKR1B10) levels in OSCC, promoting cancer stemness and leading to resistance to cisplatin (CDDP)-based chemotherapy. Materials and methodsGain- and Loss- of AKR1B10 functions were analyzed using WB and q-PCR of OSCC cells. Stemness, epithelial mesenchymal transition (EMT) markers, and CDDP drug resistance in overexpressed AKR1B10 were also identified. ResultsUpregulated AKR1B10 in OSCC significantly increased cell motility and aggregation. The results also showed that the canonical TGF-β1-Smad3 pathway was involved in arecoline-induced AKR1B10 expression, further increasing cancer stemness with CDDP resistance via the Snail-dependent EMT pathway. Moreover, oleanolic acid (OA) and ROS/RNS (reactive oxygen/nitrogen species) inhibitors effectively reversed AKR1B10-induced CDDP-resistance. ConclusionArecoline-induced ROS/RNS to hyper-activate AKR1B10 in tumor sphere cells via the TGF-β1-Smad3 pathway. Furthermore, AKR1B10 enhanced CDDP resistance in OSCC cells via EMT-inducing markers. Finally, Finally, OA may efficiently target CDDP resistance, reverse stemness in OSCC cells, and have the potential as a novel anticancer drug.

The mechanism of MMP14-positive tumor-associated fibroblast subsets in inhibiting PD-1 immunotherapy for esophageal cancer through exosomal tsRNA-10522

Esophageal cancer (EC) continues to pose a significant health risk. Cancer-associated fibroblasts (CAFs), an essential part of the tumor microenvironment (TME), are viewed as potential therapeutic targets. However, their role in tumor mechanisms specific to esophageal cancer remains to be elucidated. This study identified MMP14+ CAFs and MMP14- CAFs using immunofluorescence staining. The cytotoxic activity of CD8 T cells was assessed via western blot and ELISA. Using a transwell test, the migratory potential of MMP14+ CAFs was evaluated. Using flow cytometry, apoptosis was found in the esophageal squamous cell carcinoma cell line KYSE30. To determine the important tsRNAs released by MMP14+ CAFs, tsRNA-seq was used. Two subgroups of EC receiving PD-1 immunotherapy were identified by our research: MMP14+ CAFs and MMP14- CAFs. MMP14+ CAFs showed improved migratory capacity and released more inflammatory factors linked to cancer. Through exosomes, these CAFs may prevent anti-PD-1-treated CD8 T cells from being cytotoxic. Furthermore, exosomal tsRNA from MMP14+ CAFs primarily targeted signaling pathways connected with cancer. Notably, it was discovered that tsRNA-10522 plays a critical role within inhibiting CD8 T cell tumor cell death. The tumor cell killing of CD8 T cells by exosomal tsRNA-10522 is inhibited by a subgroup of cells called MMP14+ CAFs inside the EC microenvironment during PD-1 immunotherapy. This reduces the effectiveness of PD-1 immunotherapy for EC. Our findings demonstrate the inhibitory function of MMP14+ CAFs within EC receiving PD-1 immunotherapy, raising the prospect that MMP14+ CAFs might serve as predictive indicators in EC receiving PD-1 immunotherapy.

Iontophoresis-Enhanced Buccal Delivery of Cisplatin-Encapsulated Chitosan Nanoparticles for Treating Oral Cancer in a Mouse Model.

Cisplatin is one of the most effective chemotherapeutic drugs used in oral cancer treatment, but systemic administration has side effects. The purpose of this study was to evaluate the effect of iontophoresis on the enhancement of cisplatin release from cisplatin-encapsulated chitosan nanoparticles. The effect of different mass ratios of chitosan to tripolyphosphate (TPP) (5:1, 10:1, 15:1, 20:1) on the encapsulation efficiency of cisplatin was investigated. Uptake of cisplatin-encapsulated chitosan by cells was observed using a confocal laser scanning microscope. The cell viability at different cisplatin concentrations was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Three iontophoresis methods, namely constant-current chronopotentiometry (CCCP), cyclic chronopotentiometry (CCP), and differential pulse voltammetry (DPV), were used to enhance cisplatin release from cisplatin-encapsulated chitosan nanoparticles. In addition, mouse oral squamous cell carcinoma cell lines were implanted into the mouse oral mucosa to induce oral cancer. The effects of enhanced cisplatin release by CCCP, CCP, and DPV on tumor suppression in mice were evaluated. Tumors and lymph nodes were isolated for hematoxylin-eosin staining and immunohistochemistry staining including Ki-67 and pan CK after sacrifice. Inductively coupled plasma mass spectrometry was conducted to quantify the platinum content within the tumors. The results showed that nanoparticles with a mass ratio of 15:1 exhibited the highest cisplatin encapsulation efficiency (approximately 15.6%) and longest continued release (up to 35 days) in phosphate buffered saline with a release rate of 100%. Cellular uptake results suggested that chitosan nanoparticles were delivered to the cytoplasm via endocytosis. The results of the MTT assay revealed that the survival rate of cells decreased as the cisplatin concentration increased. The CCP (1 mA, on:off = 1 s: 1 s) and DPV (0-0.06 V) groups were the most effective in inhibiting tumor growth, and both groups exhibited the lowest percentage of Ki-67 positive and pan CK positive. This study is the first to investigate and determine the efficacy of DPV in enhancing in vivo drug release from nanoparticles for the treatment of cancer in animals. The results suggest that the CCP and DPV methods have the potential to be combined with surgery for oral cancer treatment.

Impact of Dental Pulp Stem Cell Secretome on Apoptosis, Proliferation and Drug Resistance of Head and Neck Squamous Cell Carcinoma Cell Lines: In vitro study

Impact of Dental Pulp Stem Cell Secretome on Apoptosis, Proliferation and Drug Resistance of Head and Neck Squamous Cell Carcinoma Cell Lines: In vitro study

Effect of Aspartame on viability, Morphology and Migration in Oral Squamous Cell Carcinoma Cell Line: In Vitro Study

Effect of Aspartame on viability, Morphology and Migration in Oral Squamous Cell Carcinoma Cell Line: In Vitro Study

MiRNA-199b-5p suppresses of oral squamous cell carcinoma by targeting apical-basolateral polarity via Scribble/Lgl

In epithelial cells, Scribble forms cell-cell junctions and contribute to cell morphology and homeostasis by regulating apical-basolateral polarity in mammals and functions as a tumor suppressor in many carcinomas. The initial diagnosis of oral squamous cell carcinoma is important, and its prognosis is poor when accompanied by metastasis. However, research on the mechanisms of oral squamous cell carcinoma metastasis is insufficient. Herein, we showed that Scribble regulates the apical-basolateral polarity of oral squamous cell carcinoma by regulating lethal giant larvae 1, Scribble module and E-cadherin, the adhesion junction. The expression of lethal giant larvae 1 and E-cadherin decreased when the expression of Scribble was knocked down and their localization was completely disrupted in both the oral squamous cell carcinoma cell line and in vivo model. In particular, the Scribble was involved in oral squamous cell carcinoma metastasis via hsa-miR-199b-5p, which is a microenvironmental factor of hypoxia. The disruption of Scribble localization under hypoxic conditions, but its localization was maintained in miR-199b-5p oral squamous cell carcinoma cell lines and in vivo. These results suggest that Scribble functions as a tumor suppressor marker mediated by miR-199b-5p in oral squamous cell carcinoma.

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.

The cytotoxic effect of 4 different wavelengths of Low-level laser therapy on squamous cell carcinoma – An invitro study

Background: Low-level laser therapy is a noninvasive method with the potential ability to change the balance of cell mediators and gene expressions. It affects cellular function resulting in beneficial clinical effects. This study aims to assess the effect of low-level light therapy (LLLT) using four different laser wavelengths on oral carcinoma cell viability in vitro. Methods and Material: HN5 human head and neck squamous cell carcinoma cell lines (HNSCC) were cultured and irradiated using four wavelengths of blue (485 nm), green (532nm), red (660 nm), and near Infra-red (810 nm) in a continuous mode with a dose of 1 J/cm2 (0.1W, 10sec) every 24hours for five consecutive days. Cell viability was assessed by evaluating mitochondrial activity by MTT assay. Results: All the wavelengths resulted in reduced viability of these cells compared to the controls. (P<0.05) There were statistically significant differences in cell viability between different wavelengths (P<0.001). The 810 nm laser irradiation showed the highest percentage of cell survival (55.92%) while 660 nm induced the lowest (36.02%). Conclusion: Different laser wavelengths may result in different effects on irradiated cells and red irradiation showed the lowest cell viability and the infrared laser had the highest cell viability results.