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

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.

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

Cancer ◽

10.1002/1097-0142(20001101)89:9<1966::aid-cncr13>3.0.co;2-r ◽

2000 ◽

Vol 89 (9) ◽

pp. 1966-1975 ◽

Cited By ~ 36

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

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Activation of iCaspase-9 in Neovessels Inhibits Oral Tumor Progression

Journal of Dental Research ◽

10.1177/154405910608500508 ◽

2006 ◽

Vol 85 (5) ◽

pp. 436-441 ◽

Cited By ~ 7

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.

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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

Food & Function ◽

10.1039/c8fo00865e ◽

2018 ◽

Vol 9 (7) ◽

pp. 3640-3656 ◽

Cited By ~ 3

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.

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Upregulation of LGALS1 is associated with oral cancer metastasis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835918794622 ◽

2018 ◽

Vol 10 ◽

pp. 175883591879462 ◽

Cited By ~ 7

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.

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

International Journal of Oncology ◽

10.3892/ijo.2016.3715 ◽

2016 ◽

Vol 49 (5) ◽

pp. 2011-2022 ◽

Cited By ~ 10

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

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

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i7.6 ◽

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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Abstract 4686:MALis down-regulated in oral squamous cell carcinoma and suppresses proliferation, invasion, tumorigenicity of oral cancer cells,in vitro and in vivo

10.1158/1538-7445.am10-4686 ◽

2010 ◽

Author(s):

Wantao Chen ◽

Wei Cao ◽

Ping Zhang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Oral Cancer Cells

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13-Acetoxysarcocrassolide Exhibits Cytotoxic Activity against Oral Cancer Cells through the Interruption of the Keap1/Nrf2/p62/SQSTM1 Pathway: The Need to Move Beyond Classical Concepts

Marine Drugs ◽

10.3390/md18080382 ◽

2020 ◽

Vol 18 (8) ◽

pp. 382

Author(s):

Yi-Chang Liu ◽

Bo-Rong Peng ◽

Kai-Cheng Hsu ◽

Mohamed El-Shazly ◽

Shou-Ping Shih ◽

...

Keyword(s):

Oral Cancer ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Flow Cytometric Analysis ◽

Future Application ◽

Ros Generation ◽

Dependent Manner ◽

Oral Cancer Cells ◽

Induced Apoptosis

13-Acetoxysarcocrassolide (13-AC), a marine cytotoxic product isolated from the alcyonacean coral Lobophytum crassum, exhibited potent antitumor and immunostimulant effects as reported in previous studies. However, the 13-AC antitumor mechanism of action against oral cancer cells remains unclear. The activity of 13-AC against Ca9-22 cancer cells was determined using MTT assay, flow cytometric analysis, immunofluorescence, immunoprecipitation, Western blotting, and siRNA. 13-AC induced apoptosis in oral cancer cells Ca9-22 through the disruption of mitochondrial membrane potential (MMP) and the stimulation of reactive oxygen species (ROS) generation. It increased the expression of apoptosis- and DNA damage-related proteins in a concentration- and time-dependent manner. It exerted potent antitumor effect against oral cancer cells, as demonstrated by the in vivo xenograft animal model. It significantly reduced the tumor volume (55.29%) and tumor weight (90.33%). The pretreatment of Ca9-22 cells with N-acetylcysteine (NAC) inhibited ROS production resulting in the attenuation of the cytotoxic activity of 13-AC. The induction of the Keap1-Nrf2 pathway and the promotion of p62/SQSTM1 were observed in Ca9-22 cells treated with 13-AC. The knockdown of p62 expression by siRNA transfection significantly attenuated the effect of 13-AC on the inhibition of cell viability. Our results indicate that 13-AC exerted its cytotoxic activity through the promotion of ROS generation and the suppression of the antioxidant enzyme activity. The apoptotic effect of 13-AC was found to be mediated through the interruption of the Keap1/Nrf2/p62/SQSTM1 pathway, suggesting its potential future application as an anticancer agent.

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