Protective Effects of N-Acetylcysteine against Radiation-Induced Oral Mucositis In Vitro and In Vivo / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Radiation-induced oral mucositis limits delivery of high-dose radiation to targeted cancers. Therefore, it is necessary to develop a treatment strategy to alleviate radiation-induced oral mucositis during radiation therapy. We previously reported that inhibiting reactive oxygen species (ROS) generation suppresses autophagy. Irradiation induces autophagy, suggesting that antioxidant treatment may be used to inhibit radiation-induced oral mucositis. @*Materials and Methods@#We determined whether treatment with N-acetyl cysteine (NAC) could attenuate radiation-induced buccal mucosa damage in vitro and in vivo. The protective effects of NAC against oral mucositis were confirmed by transmission electron microscopy and immunocytochemistry. mRNA and protein levels of DNA damage and autophagy-related genes were measured by quantitative real-time polymerase chain reaction and western blot analysis, respectively. @*Results@#Rats manifesting radiation-induced oral mucositis showed decreased oral intake, loss of body weight, and low survival rate. NAC intake slightly increased oral intake, body weight, and the survival rate without statistical significance. However, histopathologic characteristics were markedly restored in NAC-treated irradiated rats. LC3B staining of rat buccal mucosa revealed that NAC treatment significantly decreased the number of radiation-induced autophagic cells. Further, NAC inhibited radiation-induced ROS generation and autophagy signaling. In vitro, NAC treatment significantly reduced the expression of NRF2, LC3B, p62, and Beclin-1 in keratinocytes compared with that after radiation treatment. @*Conclusion@#NAC treatment significantly inhibited radiation-induced autophagy in keratinocytes and rat buccal mucosa and may be a potentially safe and effective option for the prevention of radiation-induced buccal mucosa damage.

Comparative Effects of Non-Thermal Atmospheric Pressure Plasma on Migration and Invasion in Oral Squamous Cell Cancer, by Gas Type

PURPOSE: The fourth state of matter, plasma is known as an ionized gas with electrons, radicals and ions. The use of non-thermal plasma (NTP) in cancer research became possible because of the progresses in plasma medicine. Previous studies on the potential NTP-mediated cancer therapy have mainly concentrated on cancer cell apoptosis. In the present study, we compared the inhibitory effect of NTP on cell migration and invasion in the oral squamous cancer cell lines. MATERIALS AND METHODS: We used oral squamous cancer cell lines (SCC1483, MSKQLL1) and different gases (N₂, He, and Ar). To investigate the mechanism of plasma treatment, using different gases (N₂, He, and Ar) which induces anti-migration and anti-invasion properties, we performed wound healing assay, invasion assay and gelatin zymography. RESULTS: The results showed that NTP inhibits cancer cell migration and invasion of oral squamous cancer cell. In addition, focal adhesion kinase expression and matrix metalloproteinase-2/9 activity were also inhibited. CONCLUSION: The suppression of cancer cell invasion by NTP varied depending on the type of gas. Comparison of the three gases revealed that N₂ NTP inhibited cell migration and invasion most potently via decreased expression of focal adhesion kinase and matrix metalloproteinase activity.

Anti-cancer Effect of Luminacin, a Marine Microbial Extract, in Head and Neck Squamous Cell Carcinoma Progression via Autophagic Cell Death / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to determine whether luminacin, a marine microbial extract from the Streptomyces species, has anti-tumor effects on head and neck squamous cell carcinoma (HNSCC) cell lines via autophagic cell death. MATERIALS AND METHODS: Inhibition of cell survival and increased cell death was measured using cell viability, colony forming, and apoptosis assays. Migration and invasion abilities of head and cancer cells were evaluated using wound healing, scattering, and invasion assays. Changes in the signal pathway related to autophagic cell death were investigated. Drug toxicity of luminacin was examined in in vitro HaCaT cells and an in vivo zebrafish model. RESULTS: Luminacin showed potent cytotoxicity in HNSCC cells in cell viability, colony forming, and fluorescence-activated cell sorting analysis. In vitro migration and invasion of HNSCC cells were attenuated by luminacin treatment. Combined with Beclin-1 and LC3B, Luminacin induced autophagic cell death in head and neck cancer cells. In addition, in a zebrafish model and human keratinocyte cell line used for toxicity testing, luminacin treatment with a cytotoxic concentration to HNSCC cells did not cause toxicity. CONCLUSION: Taken together, these results demonstrate that luminacin induces the inhibition of growth and cancer progression via autophagic cell death in HNSCC cell lines, indicating a possible alternative chemotherapeutic approach for treatment of HNSCC.

Nonthermal Plasma Induces Apoptosis in ATC Cells: Involvement of JNK and p38 MAPK-Dependent ROS

PURPOSE: To determine the effects of nonthermal plasma (NTP) induced by helium (He) alone or He plus oxygen (O2) on the generation of reactive oxygen species (ROS) and cell death in anaplastic thyroid cancer cells. MATERIALS AND METHODS: NTP was generated in He alone or He plus O2 blowing through a nozzle by applying a high alternating current voltage to the discharge electrodes. Optical emission spectroscopy was used to identify various excited plasma species. The apoptotic effect of NTP on the anaplastic thyroid cancer cell lines, such as HTH83, U-HTH 7, and SW1763, was verified with annexin V/propidium staining and TUNEL assay. ROS formation after NTP treatment was identified with fluorescence-activated cell sorting with DCFDA staining. The mitogen-activated protein kinase pathways and caspase cascade were investigated to evaluate the molecular mechanism involved and cellular targets of plasma. RESULTS: NTP induced significant apoptosis in all three cancer cell lines. The plasma using He and O2 generated more O2-related species, and increased apoptosis and intracellular ROS formation compared with the plasma using He alone. NTP treatment of SW1763 increased the expression of phosphor-JNK, phosphor-p38, and caspase-3, but not phosphor-ERK. Apoptosis of SW1763 as well as expressions of elevated phosphor-JNK, phosphor-p38, and caspase-3 induced by NTP were effectively inhibited by intracellular ROS scavengers. CONCLUSION: NTP using He plus O2 induced significant apoptosis in anaplastic cancer cell lines through intracellular ROS formation. This may represent a new promising treatment modality for this highly lethal disease.

Effects of Xanthium stramarium and Psoralea corylifolia Extracts Combined with UVA1 Irradiation on the Cell Proliferation and TGF-beta1 Expression of Keloid Fibroblasts

BACKGROUND: Xanthium stramarium (XAS) and Psoralea corylifolia (PSC), phototoxic oriental medicinal plants, has been used in traditional medicines in Asian countries. OBJECTIVE: The effects of highly purified XAS or PSC extract combined with ultraviolet A1 (UVA1) irradiation on cell proliferation and transforming growth factor-beta1 (TGF-beta1) expression of the keloid fibroblast were being investigated to define potential therapeutic uses for keloid treatments. METHODS: The keloid fibroblasts were treated with XAS or PSC alone or in the combination with UVA1 irradiation. The cell viability, apoptosis, and expression of TGF-beta1 and collagen I were investigated. RESULTS: XAS and PSC in combination with UVA1 irradiation suppressed cell proliferation and induced apoptosis of keloid fibroblasts. Furthermore, the XAS and PSC in combination with UVA1 irradiation inhibited TGF-beta1 expression and collagen synthesis in keloid fibroblasts. CONCLUSION: These findings may open up the possibility of clinically used XAS or PSC in combination with UVA1 irradiation for keloid treatments.

Effects of Xanthium stramarium and Psoralea corylifolia Extracts Combined with UVA1 Irradiation on the Cell Proliferation and TGF-beta1 Expression of Keloid Fibroblasts

BACKGROUND: Xanthium stramarium (XAS) and Psoralea corylifolia (PSC), phototoxic oriental medicinal plants, has been used in traditional medicines in Asian countries. OBJECTIVE: The effects of highly purified XAS or PSC extract combined with ultraviolet A1 (UVA1) irradiation on cell proliferation and transforming growth factor-beta1 (TGF-beta1) expression of the keloid fibroblast were being investigated to define potential therapeutic uses for keloid treatments. METHODS: The keloid fibroblasts were treated with XAS or PSC alone or in the combination with UVA1 irradiation. The cell viability, apoptosis, and expression of TGF-beta1 and collagen I were investigated. RESULTS: XAS and PSC in combination with UVA1 irradiation suppressed cell proliferation and induced apoptosis of keloid fibroblasts. Furthermore, the XAS and PSC in combination with UVA1 irradiation inhibited TGF-beta1 expression and collagen synthesis in keloid fibroblasts. CONCLUSION: These findings may open up the possibility of clinically used XAS or PSC in combination with UVA1 irradiation for keloid treatments.

Growth Inhibition and Apoptosis with H31 Metabolites from Marine Bacillus SW31 in Head and Neck Cancer Cells

OBJECTIVES: To determine whether a novel marine micro-organism with anticancer properties, H31, the metabolic product of Bacillus SW31, has anti-tumor effects on head and neck cancer, and potential for apoptotic-enhancing anti-cancer treatment of affected patients. METHODS: The cell viability and apoptosis assays were performed. Changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of H31 were explored in mouse xenograft model and drug toxicity of H31 was examined in zebrafish model. RESULTS: We identified the anticancer activity of H31, a novel metabolic product of Bacillus SW31. Bacillus SW31, a new marine micro-organism, has 70% homology with Bacillus firmus and contains potent cytotoxic bioactivity in head and neck cancer cells using MTT assay. Combined with c-JUN, p53, cytochrome C, and caspase-3, H31 induced apoptosis of KB cells, a head and neck cancer cell line. In a separate in vivo model, tumor growth in C3H/HeJ syngeneic mice was suppressed by H31. In addition, in a zebrafish model used for toxicity testing, a considerable dose of H31 did not result in embryo or neurotoxicity. CONCLUSION: Growth inhibition and apoptosis were achieved both in vitro and in vivo in head and neck cancer cells after exposure to H31, a metabolite from the marine Bacillus species, without any significant toxicity effects even at considerable H31 dose concentrations.

Green Tea Extracts Inhibits HGF-Induced HNSCC Progression in vitro / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Aberrant activation of hepatocyte growth factor (HGF) and its receptor, c-Met, has been known to be involved in many human cancer development and progression. During the search for an effective molecule inhibitor of HGF/ c-Met signaling, we have found that Epigallocatechin-3-gallate (EGCG) in green tea might inhibit HGF/c-Met signaling. Studies were performed to address whether EGCG inhibited HGF-dependent tumor proliferation and invasion in HNSCC. MATERIALS AND METHOD: For EGCG inhibition of HGF/c-Met signaling, Western blot was performed. The proliferation of FaDu cells was assayed by counting the number of the cells after treatment by HGF 0, 10 ng/ml, EGCG 1 micrometer, EGCG 10 micrometer, HGF 10+EGCG 1 micrometer, HGF 10+EGCG 10 micrometer. The dispersion of cells was observed by measuring the separation and morphologic changes of the cells after treatment with HGF 0, 10 ng/ml HGF 10+EGCG 1 micrometer, HGF 10+EGCG 10 micrometer for 24 hours. Tumor cell migration was assessed by wound healing assay and tumor cell invasiveness was assessed by the membrane invasion assay. RESULTS: HGF treatment induced rapid activation of c-Met and EGCG inhibited HGF-induced c-Met signaling in FaDu cells. HGF significantly enhanced the growth of HNSCC cells and this phenomenon was inhibited by EGCG in a dose-dependant manner (p<0.05). EGCG inhibited HGF-induced scattering, migration, and invasion of HNSCC cells in a dose-dependent manner (p<0.05). CONCLUSION: Inhibition of HGF/Met by EGCG leads to decreased proliferation, scattering, migration and invasion in vitro, suggesting the possible use of EGCG in HNSCC associated with down-regulation of HGF/Met signaling.