cytochrome-c-t and Tongue-Neoplasms

Today, it has been proven that the nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs) have widespread use in biomedical applications, for instance, in magnetic resonance imaging and targeted delivery of drugs. Despite many studies on SPIONs in diagnosing some diseases like cancer, it has not been investigated on the oral tongue squamous cell carcinoma (OTSCC) detection by the NPs. Hence, the present study has been designed to assess the in vitro cytotoxicity of SPIONs on the isolated mitochondria of OTSCC by mitochondrial tests. Isolated mitochondria were removed from the separated cancer and control tissues from the squamous cells of tango in male Wistar rats (6 or 8 weeks) and exposed to the different concentrations of SPIONs (30, 60, and 120 nM). A rise in the production of reactive oxygen species is one of the significant mechanisms of this study, followed by a collapse of mitochondrial membrane potential, the escape of mitochondrial cytochrome c, and mitochondrial swelling in the exposed isolated mitochondria of OTSCC with SPIONs. Furthermore, our results indicated that the exposure to the SPIONs reduced the activity of succinate dehydrogenase in complex II of the mitochondria obtained from cancerous oral tongue squamous. So the SPIONs can induce selective cytotoxicity on the OTSCC mitochondria without significant effects on the control mitochondria. Based on the results and further studies about in vivo experiments in this regard, it is concluded the SPIONs may be a hopeful therapeutic candidate for the treatment of OTSCC.

Topics: Animals; Antineoplastic Agents; Cytochromes c; In Vitro Techniques; Magnetic Iron Oxide Nanoparticles; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Swelling; Oxidative Stress; Rats; Reactive Oxygen Species; Squamous Cell Carcinoma of Head and Neck; Succinate Dehydrogenase; Tongue Neoplasms

Scutellariae radix is one of the most widely used anticancer herbal medicines in several Asian countries, including Korea, Japan, and China. Squamous cell carcinoma (SCC) is one of the most common head and neck carcinomas, which is highly invasive and metastatic, and can potentially develop chemoresistance. Therefore, new effective treatment methods are urgently needed. We determined the effects of Scutellariae radix on SCC-25 cells using the WST-1 assay, F-actin staining, flow cytometry analysis, immunofluorescence staining, and western blot analysis. Scutellariae radix treatment inhibited SCC-25 cell growth in a dose- and time-dependent manner, but it did not inhibit HaCaT (human keratinocyte) cell growth. Changes in cell morphology and disruption of filamentous (F)-actin organization were observed. Scutellariae radix-induced apoptosis as indicated by the translocation of cytochrome c and apoptosis-inducing factor (AIF) into the nucleus and cytosol. Scutellariae radix-induced an increase in cells with sub-G1 DNA content, and increased Bax, cleaved caspase-3, caspase-7, caspase-9, DNA fragmentation factor 45 (DFF 45), and poly(ADP-ribose) polymerase-1 (PARP-1) expression levels. Furthermore, increased expression of phosphorylated mitogen-activated protein kinase (MAPK)-related proteins was detected. The antitumor effect of Scutellariae radix was due to decreased cell proliferation, changes in cell morphology, and the activation of caspase and MAPK pathways. Taken together, the findings of this study highlight the anticancer activity of Scutellariae radix in chemoresistant SCC-25 oral squamous carcinoma cells.

Topics: Actins; Active Transport, Cell Nucleus; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Inducing Factor; Carcinoma, Squamous Cell; Caspases; Cytochromes c; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Mitogen-Activated Protein Kinases; Plant Extracts; Scutellaria baicalensis; Signal Transduction; Tongue Neoplasms; Tumor Cells, Cultured

We investigated the anti-tumor efficiency of sonodynamic therapy (SDT) on human tongue squamous carcinoma SAS cell line using low intensity ultrasound (LIU) of 0.6 and 0.8 W/cm(2), plus 5-aminolevulinic acid (ALA). Xenograft in vivo experiments using Balb/ca nude mice and MTT assays in vitro showed that ALA-LIU therapy significantly suppressed the proliferation of SAS cells. ALA-LIU therapy markedly enhanced SAS cell apoptosis rate compared to LIU alone. Based on TEM and fluorescence microscopy observations, there are notably morphology changes and seriously swollen mitochondria in xenograft tissues, and ALA-induced PpIX bond strongly to mitochondria of SAS cells. Immunohistochemical staining and western blotting demonstrated upregulation of Bax, cytochrome c and caspase-3, and downregulation of Bcl-2 for both in vivo and in vitro cases after ALA-LIU treatment. Increase of reactive oxygen species (ROS) in the ALA-LIU treatment groups were found using 2, 7-dichlorofluorescin diacetate (DCFH-DA) staining. Administration of the ROS scavenger, N-acetylcysteine (NAC), suppressed ALA-LIU-induced apoptosis and the expression of mitochondria apoptosis-related proteins, which confirmed that the ALA-LIU induced SAS cell apoptosis is through the generation of ROS. The process initially damaged mitochondria, activated pro-apoptotic factors Bax and cytochrome c and suppressed the anti-apoptotic factor Bcl-2, activated caspase-3 to executed apoptosis through mitochondrial signaling pathway.

Topics: Aminolevulinic Acid; Animals; Apoptosis; bcl-2-Associated X Protein; Calcium; Carcinoma, Squamous Cell; Caspase 3; Cell Line, Tumor; Cytochromes c; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Photosensitizing Agents; Proto-Oncogene Proteins c-bcl-2; Protoporphyrins; Reactive Oxygen Species; Tongue Neoplasms; Transplantation, Heterologous; Ultrasonic Therapy

Histone deacetylases (HDACs) inhibitors induce cell growth arrest and apoptosis in a wide variety of tumor cells. The purpose of this study was to evaluate the effects of trichostatin A (TSA), one of the HDACs inhibitors, on proliferation and apoptosis of oral squamous cell carcinoma cells. Exposure of Tca83 cells (established from human tongue squamous cell carcinoma) to TSA resulted in cell growth inhibition and apoptosis in a dose-dependent manner as measured with MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and DAPI (4'6'diamidino-2-phenylindole dihydrochloride) staining. Western blot showed that both total PTEN and membrane-bound PTEN were induced by TSA treatment, whereas phosphorylation level (Ser 473) of AKT was correspondingly down-regulated by TSA treatment. Knock-down of PTEN expression with PTEN siRNA could sufficiently block 0.25mug/ml TSA induced inhibition of cell growth, but failed to block 0.5mug/ml TSA induced inhibition of cell growth and apoptosis. Moreover, induction of apoptosis by TSA treatment was also demonstrated by cytochrome C releasing and induction of caspase-3. Conclusively, the results suggested that PTEN/AKT pathway was involved in TSA induced cell growth inhibition and apoptosis of oral squamous cell carcinoma cells. HDACs inhibitors could be potential anticancer drugs for chemotherapy of oral squamous cell carcinoma.

Topics: Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cytochromes c; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Indoles; Neoplasm Proteins; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Thiazoles; Tongue Neoplasms