scholarly journals CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Ai ◽  
Yu Dou ◽  
Zhaodi Nan ◽  
Ketao Wang ◽  
Huayang Wang ◽  
...  
Keyword(s):  
Retrospective Cohort ◽  
Squamous Carcinoma ◽  
Macrophage Infiltration ◽  
Poly I:C ◽  
Poor Overall Survival ◽  
Macrophage Recruitment ◽  
Therapy Strategy ◽  
Oral Squamous Carcinoma ◽  
Hpv Status

Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.

scholarly journals Tumor protein D52 is upregulated in oral squamous carcinoma cells under hypoxia in a hypoxia-inducible-factor-independent manner and is involved in cell death resistance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuzo Abe ◽  
Yoshiki Mukudai ◽  
Mai Kurihara ◽  
Asami Houri ◽  
Junichiro Chikuda ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Squamous Carcinoma ◽  
Cancer Therapeutics ◽  
Tumor Xenograft ◽  
Independent Manner ◽  
Protein Levels ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

Abstract Background Tumor protein D52 (TPD52) reportedly plays an important role in the proliferation and metastasis of various cancer cells, including oral squamous cell carcinoma (OSCC) cells, and is expressed strongly at the center of the tumor, where the microenvironment is hypoxic. Thus, the present study investigated the roles of TPD52 in the survival and death of OSCC cells under hypoxia, and the relationship with hypoxia-inducible factor (HIF). We examined the expression of TPD52 in OSCC cells under hypoxic conditions and analyzed the effects of HIF on the modulation of TPD52 expression. Finally, the combinational effects of TPD52 knockdown and HIF inhibition were investigated both in vitro and in vivo. Results The mRNA and protein levels of TPD52 increased in OSCC cells under hypoxia. However, the increase was independent of HIF transcription. Importantly, the observation was due to upregulation of mRNA stability by binding of mRNA to T-cell intercellular antigen (TIA) 1 and TIA-related protein (TIAR). Simultaneous knockdown of TPD52 and inhibition of HIF significantly reduced cell viability. In addition, the in vivo tumor-xenograft experiments showed that TPD52 acts as an autophagy inhibitor caused by a decrease in p62. Conclusions This study showed that the expression of TPD52 increases in OSCC cells under hypoxia in a HIF-independent manner and plays an important role in the proliferation and survival of the cells in concordance with HIF, suggesting that novel cancer therapeutics might be led by TPD52 suppression.

scholarly journals Tumor Protein D52 Is Upregulated in Oral Squamous Carcinoma Cells Under Hypoxia in a Hypoxia-inducible-factor-independent Manner and Is Involved in Cell Death Resistance

2021 ◽  
Author(s):  
Yuzo Abe ◽  
Yoshiki Mukudai ◽  
Mai Kurihara ◽  
Asami Houri ◽  
Junichiro Chikuda ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Squamous Carcinoma ◽  
Cancer Therapeutics ◽  
Tumor Xenograft ◽  
Independent Manner ◽  
Protein Levels ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

Abstract Background. Tumor protein D52 (TPD52) reportedly plays an important role in the proliferation and metastasis of various cancer cells, including oral squamous cell carcinoma (OSCC) cells, and is expressed strongly at the center of the tumor, where the microenvironment is hypoxic. Thus, the present study investigated the roles of TPD52 in the survival and death of OSCC cells under hypoxia, and the relationship with hypoxia-inducible factor (HIF). We examined the expression of TPD52 in OSCC cells under hypoxic conditions and analyzed the effects of HIF on the modulation of TPD52 expression. Finally, the combinational effects of TPD52 knockdown and HIF inhibition were investigated both in vitro and in vivo.Results. The mRNA and protein levels of TPD52 increased in OSCC cells under hypoxia. However, the increase was independent of HIF transcription. Importantly, the observation was due to upregulation of mRNA stability by binding of mRNA to T-cell intercellular antigen (TIA) 1 and TIA-related protein (TIAR). Simultaneous knockdown of TPD52 and inhibition of HIF significantly reduced cell viability. In addition, the in vivo tumor-xenograft experiments showed that TPD52 acts as an autophagy inhibitor caused by a decrease in p62.Conclusions. This study showed that the expression of TPD52 increases in OSCC cells under hypoxia in a HIF-independent manner and plays an important role in the proliferation and survival of the cells in concordance with HIF, suggesting that novel cancer therapeutics might be led by TPD52 suppression.

scholarly journals Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells

2020 ◽  
Vol 475 (1-2) ◽  
pp. 119-126
Author(s):  
Shian-Ren Lin ◽  
Chun-Shu Lin ◽  
Ching-Cheng Chen ◽  
Feng-Jen Tseng ◽  
Tsung-Jui Wu ◽  
...  
Keyword(s):  
Squamous Carcinoma ◽  
Human Kidney ◽  
Carcinoma Cells ◽  
Heart Cells ◽  
Slight Reduction ◽  
Normal Cells ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma ◽  
Metabolic Reduction

Abstract Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox’s cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox’s effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

MicroRNA-378-3p/5p suppresses the migration and invasiveness of oral squamous carcinoma cells by inhibiting KLK4 expression

2020 ◽  
Vol 98 (2) ◽  
pp. 154-163
Author(s):  
Zhi Cui ◽  
Shiqun Sun ◽  
Qilin Liu ◽  
Xuechun Zhou ◽  
Siyu Gao ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Squamous Carcinoma ◽  
Effective Measure ◽  
Mesenchymal Transition ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma ◽  
In Cells

Distant metastasis frequently occurs in oral squamous cell carcinoma (OSCC) and contributes to the adverse prognosis for patients with OSCC. However, the potential mechanisms behind the metastasis have not yet been clarified. This study investigated the role of miR-378 in the migration and invasiveness of OSCC in vitro and in vivo. According to our results, the migration and invasiveness of OSCC cells were increased in cells overexpressing miR-378, and reduced in cells where miR-378-3p/5p was silenced. In addition, overexpression of miR-378 suppressed the expressions and activities of matrix metalloproteinase 9 (MMP-9) and MMP-2. Epithelial–mesenchymal transition (EMT) was restrained by overexpression of miR-378, as evidenced by an increase in E-cadherin expression and decrease in N-cadherin and uPA expression. However, knockdown of miR-378-3p/5p produced the opposite results. Moreover, kallikrein-related peptidase 4 (KLK4) was confirmed to be a target gene of miR-378. Overexpression of KLK4 reversed the induced decrease in migration and invasiveness of cells overexpressing miR-378 by upregulating the levels of MMP-9, MMP-2, and N-cadherin, and downregulating the level of E-cadhrin. Finally, the number of metastasis nodules in the lung tissues of nude mice was reduced by overexpression of miR-378, whereas the number of metastases increased with knockdown of miR-378. Taken together, our results suggest that the miR-378–KLK4 axis is involved in the mechanisms behind the migration and invasiveness of OSCC cells. Targeting the miR-378–KLK4 axis may be an effective measure for treating OSCC.

scholarly journals Evaluation of Anti Carcinogenic Activity of Trifolium pratense on Oral Cancer Cell- An in vitro Study

2021 ◽  
pp. 800-806
Author(s):  
V. A. Muralidharan ◽  
R. V. Geetha
Keyword(s):  
Oral Cancer ◽  
Inhibitory Activity ◽  
Trifolium Pratense ◽  
Linear Regression Analysis ◽  
Squamous Carcinoma ◽  
Carcinoma Cells ◽  
Carcinogenic Activity ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

Introduction: Trifolium pratense also known as the red clover is widely distributed in the tropics and in the subtropical regions. It is generally consumed in the form of tea by the northern states of India and some tribal people of Nepal and Bhutan. Studies reveal that it is rich in antioxidant and anti-inflammatory activity. It is due to the presence of unique isoflavones found in Trifolium pratense are Biohanin A and formononetin. Aim: The main aim of the study is to find out whether Trifolium pratense extract has antiproliferative activity against oral squamous carcinoma cells. Materials and Methods: The  dried buds of Trifolium pratense flowers  were purchased commercially and then powdered  Then MTT assays  was carried out to find out it’s inhibitory activity against oral carcinoma cells Results and Discussion: From the assay it is evident that it shows a potent inhibitory activity against oral squamous carcinoma cells. Linear regression analysis revealed that the IC50 was found to be at 53.13µg/ml which is higher than that of other species of this family. Conclusion: From the above study it is evident that Trifolium pratense has a very good inhibitory activity and hence can be used in the treatment of oral cancer.

scholarly journals Loss of Caspase-8 function in combination with SMAC mimetic treatment sensitizes Head and Neck Squamous Carcinoma to radiation through induction of necroptosis

2020 ◽  
Author(s):  
Burak Uzunparmak ◽  
Meng Gao ◽  
Antje Lindemann ◽  
Kelly Erikson ◽  
Li Wang ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Carcinoma ◽  
Caspase 8 ◽  
Poor Overall Survival ◽  
Syngeneic Mouse ◽  
Syngeneic Mouse Model ◽  
Key Enzyme ◽  
Smac Mimetic ◽  
Unique Cell

AbstractCaspase-8 (CASP8) is one of the most frequently mutated genes in head and neck squamous carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a unique cell death mechanism. Here, we evaluated how CASP8 regulates necroptosis in HSNCC using cell line models and syngeneic mouse xenografts. In vitro, knockdown of CASP8 rendered HNSCCs susceptible to necroptosis induced by a second mitochondria-derived activator of caspase (SMAC) mimetic, Birinapant, when combined with pan-caspase inhibitors Z-VAD-FMK or Emricasan. Strikingly, inhibition of CASP8 function via knockdown or Emricasan treatment was associated with enhanced radiation killing by Birinapant through induction of necroptosis. In a syngeneic mouse model of oral cancer, Birinapant, particularly when combined with radiation delayed tumor growth and enhanced survival under CASP8 loss. Exploration of molecular underpinnings of necroptosis sensitivity confirmed that the level of functional receptor-interacting serine/threonine-protein kinase-3 (RIP3), a key enzyme in the necroptosis pathway was crucial in determining susceptibility to this mode of death. Although an in vitro screen revealed that many HNSCC cell lines were resistant to necroptosis due to low levels of RIP3, patient tumors maintain RIP3 expression and should therefore remain sensitive. Collectively, these results suggest that targeting the necroptosis pathway with SMAC mimetics, especially in combination with radiation, may be a relevant therapeutic approach in HNSCC with compromised CASP8 status, provided that RIP3 function is maintained.SignificanceCASP8 status regulates necroptotic death in HNSCC and this pathway can be exploited therapeutically.

scholarly journals Potential Anticancer Activity against Human Epithelial Cancer Cells of Peumus Boldus Leaf Extract

2008 ◽  
Vol 3 (12) ◽  
pp. 1934578X0800301 ◽  
Author(s):  
Juan Garbarino ◽  
Nicolas Troncoso ◽  
Giuseppina Frasca ◽  
Venera Cardile ◽  
Alessandra Russo
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Human Cancer ◽  
Squamous Carcinoma ◽  
Lactic Dehydrogenase ◽  
Kb Cells ◽  
Membrane Breakdown ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma

The potential in vitro antineoplastic effect has been studied of a methanolic extract of leaves of Peumus boldus Molina (Monimiaceae) on two human cancer epithelial cell lines, DU-145 cells (androgen-insensitive prostate cancer cells) and KB cells (oral squamous carcinoma cells). Our findings show that this extract exhibited comparable effects on the cancer cells examined as judged by IC50 values (5.07±0.4 μg/mL and 5.28±0.5 μg/mL in DU-145 and KB cells, respectively). In addition, with respect to genomic DNA damage, determined by Comet assay, the results obtained show a high fragmentation of DNA, not correlated to lactic dehydrogenase (LDH) release, a marker of membrane breakdown, in both cell lines treated with the extract at 5–20 μg/mL concentrations. Taken together, our experimental evidence may justify further investigation of the chemopreventive and chemotherapeutic potential of this natural drug.

Sign in / Sign up

Export Citation Format

Share Document