scholarly journals GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells

2020 ◽  
Vol 21 (17) ◽  
pp. 6076
Author(s):  
Taís Bacelar Sacramento de Araújo ◽  
Leonardo de Oliveira Siquara da Rocha ◽  
Manuela Torres Andion Vidal ◽  
Paulo Lucas Cerqueira Coelho ◽  
Mitermayer Galvão dos Reis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Squamous Cell ◽  
Nuclear Fragmentation

Due to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the effects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against different tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC50: 36 µM) to the tested compound. The compound’s effects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.

scholarly journals Radiation Sensitization of Basal Cell and Head and Neck Squamous Cell Carcinoma by the Hedgehog Pathway Inhibitor Vismodegib

2018 ◽  
Vol 19 (9) ◽  
pp. 2485 ◽  
Author(s):  
Stephanie Hehlgans ◽  
Patrick Booms ◽  
Ömer Güllülü ◽  
Robert Sader ◽  
Claus Rödel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Squamous Cell ◽  
Hedgehog Signaling ◽  
Cell Cycle Distribution ◽  
Hedgehog Signaling Pathway

Vismodegib, an inhibitor of the Hedgehog signaling pathway, is an approved drug for monotherapy in locally advanced or metastatic basal cell carcinoma (BCC). Data on combined modality treatment by vismodegib and radiation therapy, however, are rare. In the present study, we examined the radiation sensitizing effects of vismodegib by analyzing viability, cell cycle distribution, cell death, DNA damage repair and clonogenic survival in three-dimensional cultures of a BCC and a head and neck squamous cell carcinoma (HNSCC) cell line. We found that vismodegib decreases expression of the Hedgehog target genes glioma-associated oncogene homologue (GLI1) and the inhibitor of apoptosis protein (IAP) Survivin in a cell line- and irradiation-dependent manner, most pronounced in squamous cell carcinoma (SCC) cells. Furthermore, vismodegib significantly reduced proliferation in both cell lines, while additional irradiation only slightly further impacted on viability. Analyses of cell cycle distribution and cell death induction indicated a G1 arrest in BCC and a G2 arrest in HNSCC cells and an increased fraction of cells in SubG1 phase following combined treatment. Moreover, a significant rise in the number of phosphorylated histone-2AX/p53-binding protein 1 (γH2AX/53BP1) foci in vismodegib- and radiation-treated cells was associated with a significant radiosensitization of both cell lines. In summary, these findings indicate that inhibition of the Hedgehog signaling pathway may increase cellular radiation response in BCC and HNSCC cells.

scholarly journals α-Mangostin Induces Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cell

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hyun-Ho Kwak ◽  
In-Ryoung Kim ◽  
Hye-Jin Kim ◽  
Bong-Soo Park ◽  
Su-Bin Yu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Cycle Arrest ◽  
Squamous Cell ◽  
G1 Phase ◽  
Cycle Arrest ◽  
Related Proteins

Mangosteen has long been used as a traditional medicine and is known to have antibacterial, antioxidant, and anticancer effects. Although the effects ofα-mangostin, a natural compound extracted from the pericarp of mangosteen, have been investigated in many studies, there is limited data on the effects of the compound in human oral squamous cell carcinoma (OSCC). In this study,α-mangostin was assessed as a potential anticancer agent against human OSCC cells.α-Mangostin inhibited cell proliferation and induced cell death in OSCC cells in a dose- and time-dependent manner with little to no effect on normal human PDLF cells.α-Mangostin treatment clearly showed apoptotic evidences such as nuclear fragmentation and accumulation of annexin V and PI-positive cells on OSCC cells.α-Mangostin treatment also caused the collapse of mitochondrial membrane potential and the translocation of cytochrome c from the mitochondria into the cytosol. The expressions of the mitochondria-related proteins were activated byα-mangostin. Treatment withα-mangostin also induced G1 phase arrest and downregulated cell cycle-related proteins (CDK/cyclin). Hence,α-mangostin specifically induces cell death and inhibits proliferation in OSCC cells via the intrinsic apoptosis pathway and cell cycle arrest at the G1 phase, suggesting thatα-mangostin may be an effective agent for the treatment of OSCC.

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

2019 ◽  
Vol 19 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Ling Gao ◽  
Jianwei Dong ◽  
Nanyang Zhang ◽  
Zhanxian Le ◽  
Wenhao Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cyclosporine A ◽  
Migration And Invasion ◽  
Signal Molecules ◽  
Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

scholarly journals Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 (10) ◽  
pp. 4559
Author(s):  
Jinyoung Park ◽  
Yoon-Seo Jang ◽  
Jeong-Hae Choi ◽  
Miheon Ryu ◽  
Gyoo-Cheon Kim ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nonthermal Plasma ◽  
Therapeutic Effects ◽  
Hacat Cells ◽  
Plasma Therapy

Combination therapies for the treatment of oral squamous cell carcinoma have been studied extensively and represent a synergistic approach with better outcomes than monotherapy. In this study, a novel combination therapy was investigated using gold nanoparticles (GNP) conjugated to programmed cell death protein ligand 1 (PD-L1) antibodies and nonthermal plasma (NTP). The present study describes the effectiveness of NTP using PD-L1 antibody conjugated to GNP in PD-L1 expressing SCC-25 cells, an oral squamous cell carcinoma line. Immunocytochemistry revealed higher levels of PD-L1 expression and an increase in the selective uptake of PD-L1 antibody + GNP on SCC-25 cells compared to HaCaT cells. In addition, cell viability analyses confirmed higher levels of cell death of SCC-25 cells after treatment with PD-L1 antibody, GNP, and NTP compared to HaCaT cells. Among the experimental groups, the highest cell death was observed upon treatment with PD-L1 antibody + GNP + NTP. Following the Western blot analysis and immunofluorescence staining, the expression of apoptosis-related proteins was found to increase after treatment with PD-L1 antibody + GNP + NTP among the other experimental groups. In conclusion, the treatment of SCC-25 cells with PD-L1 antibody + GNP + NTP significantly increased the number of dead cells compared to other experimental groups. The results of this in vitro study confirmed the therapeutic effects of PD-L1 antibody + GNP + NTP treatment on oral squamous cell carcinoma.

scholarly journals Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 55057-55068 ◽  
Author(s):  
Talita Antunes Guimarães ◽  
Lucyana Conceição Farias ◽  
Eliane Sobrinho Santos ◽  
Carlos Alberto de Carvalho Fraga ◽  
Lissur Azevedo Orsini ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hypoxic Conditions
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