scholarly journals Activation of iCaspase-9 in Neovessels Inhibits Oral Tumor Progression

2006 ◽  
Vol 85 (5) ◽  
pp. 436-441 ◽  
Author(s):  
M.S. Pinsky ◽  
W. Song ◽  
Z. Dong ◽  
K. Warner ◽  
B. Zeitlin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oral Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immunodeficient Mice ◽  
Oral Tumor ◽  
Biodegradable Scaffolds ◽  
Oral Tumors ◽  
Oral Cancer Cells

Tumors of the oral cavity are highly vascularized malignancies. Disruption of neovascular networks was shown to limit the access of nutrients and oxygen to tumor cells and inhibit tumor progression. Here, we evaluated the effect of the activation of an artificial death switch (iCaspase-9) expressed in neovascular endothelial cells on the progression of oral tumors. We used biodegradable scaffolds to co-implant human dermal microvascular endothelial cells stably expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells expressing luciferase (OSCC3-luc or UM-SCC-17B-luc) in immunodeficient mice. Alternatively, untransduced HDMEC were co-implanted with oral cancer cells, and a transcriptionaly targeted adenovirus (Ad-VEGFR2-iCasp-9) was injected locally to deliver iCaspase-9 to neovascular endothelial cells. In vivo bioluminescence demonstrated that tumor progression was inhibited, and immunohistochemistry showed that microvessel density was decreased, when iCaspase-9 was activated in tumor-associated microvessels. We conclude that activation of iCaspase-9 in neovascular endothelial cells is sufficient to inhibit the progression of xenografted oral tumors.

scholarly journals Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7509
Author(s):  
Hai Huang ◽  
Jun-Koo Yi ◽  
Su-Geun Lim ◽  
Sijun Park ◽  
Haibo Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Migration And Invasion ◽  
Oxygen Species ◽  
Oral Cancer Cells

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.

Mechanism for bone invasion of oral cancer cells mediated by interleukin‐6 in vitro and in vivo

Cancer ◽  
2000 ◽  
Vol 89 (9) ◽  
pp. 1966-1975 ◽  
Author(s):  
Masato Okamoto ◽  
Kenji Hiura ◽  
Go Ohe ◽  
Yasuo Ohba ◽  
Kunihoro Terai ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Interleukin 6 ◽  
Bone Invasion ◽  
Oral Cancer Cells

Sensory acceptable equivalent doses of β-phenylethyl isothiocyanate (PEITC) induce cell cycle arrest and retard the growth of p53 mutated oral cancer in vitro and in vivo

2018 ◽  
Vol 9 (7) ◽  
pp. 3640-3656 ◽  
Author(s):  
Aroonwan Lam-ubol ◽  
Alison Lea Fitzgerald ◽  
Arnat Ritdej ◽  
Tawaree Phonyiam ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Oral Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Oral Cancer Cells ◽  
Phenylethyl Isothiocyanate

Sensory acceptable doses of PEITC are selectively toxic to oral cancer cells via ROS-mediated cell cycle arrest.

scholarly journals Upregulation of LGALS1 is associated with oral cancer metastasis

2018 ◽  
Vol 10 ◽  
pp. 175883591879462 ◽  
Author(s):  
Ji-Min Li ◽  
Chien-Wei Tseng ◽  
Chi-Chen Lin ◽  
Ching-Hsuan Law ◽  
Yu-An Chien ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Mapk Pathway ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Oral Cancer Cells

Background: Oral cancer metastasis is a devastating process that contributes to poor prognosis and high mortality, yet its detailed underlying mechanisms remain unclear. Here, we aimed to evaluate metastasis-specific markers in oral cancer and to provide comprehensive recognition concerning functional roles of the specific target in oral cancer metastasis. Methods: Lectin, galactoside-binding, soluble, 1 (LGALS1) was identified by secretomic analysis. LGALS1 expression of patient samples with oral cancer on the tissue microarray were examined by immunochemical (IHC) staining. Small interfering RNA (siRNA)-mediated knockdown of LGALS1 revealed the role of LGALS1 in oral cancer metastasis in vitro and in vivo. Results: LGALS1 was observed to be upregulated in highly invasive oral cancer cells, and elevated LGALS1 expression was correlated with cancer progression and lymph node metastasis in oral cancer tissue specimens. Functionally, silencing LGALS1 resulted in suppressed cell growth, wound healing, cell migration, and cell invasion in oral cancer cells in vitro. Knockdown of LGALS1 in highly invasive oral cancer cells dramatically inhibited lung metastasis in an in vivo mouse model. Mechanistic studies suggested p38 mitogen-activated protein kinase (MAPK) phosphorylation, upregulated MMP-9, and mesenchymal phenotypes of epithelial-mesenchymal transition (EMT) in highly invasive oral cancer cells, whereas siRNA against LGALS1 resulted in the inactivation of p38 MAPK pathway, downregulated MMP-9, and EMT inhibition. Conclusions: These findings demonstrate that elevated LGALS1 is strongly correlated with oral cancer progression and metastasis, and that it could potentially serve as a prognostic biomarker and an innovative target for oral cancer therapy.

scholarly journals Targeting all transforming growth factor-β isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer

2020 ◽  
Vol 295 (36) ◽  
pp. 12559-12572
Author(s):  
Kazuki Takahashi ◽  
Yuichi Akatsu ◽  
Katarzyna A. Podyma-Inoue ◽  
Takehisa Matsumoto ◽  
Hitomi Takahashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Oral Cancer ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Oral Cancer Cells ◽  
Tgf Β1

Tumor progression is governed by various growth factors and cytokines in the tumor microenvironment (TME). Among these, transforming growth factor-β (TGF-β) is secreted by various cell types residing in the TME and promotes tumor progression by inducing the epithelial-to-mesenchymal transition (EMT) of cancer cells and tumor angiogenesis. TGF-β comprises three isoforms, TGF-β1, -β2, and -β3, and transduces intracellular signals via TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII). For the purpose of designing ligand traps that reduce oncogenic signaling in the TME, chimeric proteins comprising the ligand-interacting ectodomains of receptors fused with the Fc portion of immunoglobulin are often used. For example, chimeric soluble TβRII (TβRII-Fc) has been developed as an effective therapeutic strategy for targeting TGF-β ligands, but several lines of evidence indicate that TβRII-Fc more effectively traps TGF-β1 and TGF-β3 than TGF-β2, whose expression is elevated in multiple cancer types. In the present study, we developed a chimeric TGF-β receptor containing both TβRI and TβRII (TβRI-TβRII-Fc) and found that TβRI-TβRII-Fc trapped all TGF-β isoforms, leading to inhibition of both the TGF-β signal and TGF-β–induced EMT of oral cancer cells, whereas TβRII-Fc failed to trap TGF-β2. Furthermore, we found that TβRI-TβRII-Fc suppresses tumor growth and angiogenesis more effectively than TβRII-Fc in a subcutaneous xenograft model of oral cancer cells with high TGF-β expression. These results suggest that TβRI-TβRII-Fc may be a promising tool for targeting all TGF-β isoforms in the TME.

scholarly journals Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo

Oral Oncology ◽  
2017 ◽  
Vol 72 ◽  
pp. 123-131 ◽  
Author(s):  
Angela A. Alexander-Bryant ◽  
Haiwen Zhang ◽  
Christopher C. Attaway ◽  
William Pugh ◽  
Laurence Eggart ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Oral Cancer Cells

scholarly journals Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo

2016 ◽  
Vol 49 (5) ◽  
pp. 2011-2022 ◽  
Author(s):  
Xiaoli Ji ◽  
Zhihui Zhang ◽  
Ying Han ◽  
Jiangyuan Song ◽  
Xiangliang Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Gingival Tissue ◽  
Oral Cancer Cells

scholarly journals Spontaneous emergence of non-convertible cell states with CD24-High phenotype results in phenotypic heterogeneity that associates with poor prognosis in oral cancer

2021 ◽  
Author(s):  
Kavya Vipparthi ◽  
Kishore Hari ◽  
Priyanka Chakraborty ◽  
Subhashis Ghosh ◽  
Ankit Kumar Patel ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Aldh Activity ◽  
Induced Stress ◽  
Response To Chemotherapy ◽  
Oral Tumors ◽  
Alternate States ◽  
Oral Cancer Cells

AbstractCancer cells within individual tumors often exist in distinct phenotypic states contributing to intratumoral heterogeneity (ITH). However, studies on cell state dynamics among oral cancer cells are largely missing. Here, we have multiplexed phenotypic markers of putative oral-stem-like cancer cells (SLCCs) and characterized diversity among CD44-positive oral cancer cell subpopulations with respect to distinct expression of CD24 and aldehyde dehydrogenase (ALDH)-activity. Our in vitro experimental observations were explained by a Markov model where subpopulations followed two distinct patterns of spontaneous repopulation dynamics. Cells showed stochastic inter-conversions on ALDH-axis, harnessed by cancer cells to enrich ALDHHigh subpopulations in response to Cisplatin treatment. However, these cells followed a strict non-interconvertible transition of CD24Low to CD24High subpopulations, even in response to chemotherapy-induced stress. Using phenotype-specific RNAseq, we suggest the organization of subpopulations into hierarchical structure with possible maintenance of intermediate alternate states of stemness within the differentiating oral cancer cells. We also show that the population dynamics described here may influence tumor behaviour by increasing ITH in aggressive oral tumors. Overall, the described phenotypic subgroups not only reliably exhibited spontaneous or Cisplatin-driven cellular dynamics but also the distinct transcription states of oral cancer cells. Most importantly, our in vitro model system derived observations emphasized the prognostic power which may be translated for betterment of oral cancer patients.Graphical AbstractWe have characterized diversity among CD44-positive oral cancer cells lines with respect to distinct expression of CD24 and ALDH-activity. Cells showed stochastic inter-conversions on ALDH-axis but a strict non-interconvertible transition of CD24Low to CD24High phenotype, even in response to chemotherapy-induced stress. RNAseq study suggested the organization of subpopulations into hierarchical structure with possible maintenance of intermediate alternate states of stemness within the differentiating oral cancer cells. The described population dynamics may influence tumor behaviour by increasing intratumoral heterogeneity in aggressive oral tumors.

scholarly journals Tiazofurin inhibits oral cancer growth in vitro and in vivo via upregulation of miR-204 expression

2020 ◽  
Vol 19 (7) ◽  
pp. 1377-1382
Author(s):  
Xiaoying Tang ◽  
Aimin Zhao ◽  
Yanhuan Hong
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Cancer Growth ◽  
Caspase 9 ◽  
Diphenyltetrazolium Bromide ◽  
Oral Cancer Cells

Purpose: To investigate the effect of tiazofurin on proliferation and growth of oral cancer cells, and the associated mechanism(s) of action.Methods: The effect of tiazofurin on the cytotoxicity of SCC-VII and SCC-25 oral cancer cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while cell apoptosis was determined by flow cytometry. Western blotting was used for assaying proteinexpressions.Results: Tiazofurin inhibited the viability of the oral cancer cells in a concentration-based manner (p < 0.05). Tiazofurin treatment at a dose of 2.0 μM reduced the proliferation of SCC-VII and SCC-25 cells to 25 and 22 %, respectively. Apoptosis was significantly increased in SCC-VII and SCC-25 cells by tiazofurin treatment, relative to untreated cells (p < 0 .05). Tiazofurin also increased the activation levels of caspase-3 and caspase-9 and downregulated the expressions of p-Akt and p-mTOR in the two cancer cell lines. Moreover, miR-204 expression was significantly promoted in the tiazofurin-treated cells, when compared to control (p < 0 .05). In SCC-VII cells, treatment with tiazofurin suppressed Factin expression, relative to control.Conclusion: These results demonstrate that tiazofurin inhibits the viability and proliferation of SCC-VII and SCC-25 cancer cells via induction of apoptosis and activation of caspase-3/caspase-9. Moreover, tiazofurin targets Akt/mTOR pathway, and upregulats the expressions of F-actin and miR-204 in the oral carcinoma cells. These findings suggest that tiazofurin has a potential for use as an effective treatment for oral cancer. Keywords: Oral cancer, Tiazofurin, Apoptosis, Caspase, Cytotoxicity

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