scholarly journals In Vitro Growth Effects of Morphine and Naloxone on Various Head and Neck Squamous Cell Cancer Cell Lines

2018 ◽  
Author(s):  
Stephen R Denton ◽  
Reema Padia ◽  
Jill E. Shea ◽  
Luke O Buchmann ◽  
Gregory J Stoddard ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Significant Inhibition ◽  
Base Of Tongue ◽  
Inhibition Of Growth ◽  
Mu Antagonist

AbstractUnderstanding the potential effects of mu-agonism and antagonism on cancer cells is important for the perioperative physician. Previous studies suggest some tumor cells may have altered growth with mu-agonism or antagonism. This study investigates the effects of morphine (mu-agonist) and naloxone (mu-antagonist) in head and neck tumor cell lines (laryngeal squamous cell carcinoma (SCC), lateral tongue SCC and base of tongue SCC). Morphine showed no significant effect on tumor cell growth. Naloxone showed significant inhibition of growth in laryngeal SCC, but not in lateral or base of tongue SCC.

scholarly journals Deguelin Induces Apoptosis by Targeting Both EGFR-Akt and IGF1R-Akt Pathways in Head and Neck Squamous Cell Cancer Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yuh Baba ◽  
Masato Fujii ◽  
Toyonobu Maeda ◽  
Atsuko Suzuki ◽  
Satoshi Yuzawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Akt Activation ◽  
Igf1r Signaling ◽  
Induced Apoptosis

Deguelin, a rotenoid compound from the African plantMundulea sericea(Leguminosae), has been shown to possess antitumor activities but the exact role for the growth factor receptor mediated signaling pathway in head and neck squamous cell carcinoma (HNSCC) is currently still unclear. In the present study, we investigated the effect of deguelin on epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF1R) pathways in HNSCC cell lines. Flowcytometric analysis revealed accumulation of annexin V positivity in deguelin-treated cells, showing that deguelin induced apoptosis. The deguelin-induced apoptosis was accompanied by the reduction of constitutive phosphorylated levels of IGF1R, Akt, and extracellular signal-regulated kinase1/2 (ERK1/2). LY294002-mediated inhibition of phosphatidylinositol-3 kinase, which is an upstream effector for Akt activation, increased cleavage of poly(ADP-ribosyl) polymerase (PARP) but ERK inhibition by U0126 did not. Deguelin inhibited both IGF-1- and EGF-induced Akt activation. These results showed that deguelin possessed antitumor effect by targeting Akt in dual axis such as EGFR and IGF1R signaling pathways and suggested that it provides an applicable therapeutic strategy for HNSCC patients.

scholarly journals Radiosensitizing effect of galunisertib, a TGF-ß receptor I inhibitor, on head and neck squamous cell carcinoma in vitro

2022 ◽  
Author(s):  
Bernhard J. Jank ◽  
Teresa Lenz ◽  
Markus Haas ◽  
Lorenz Kadletz-Wanke ◽  
Nicholas J. Campion ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Metabolic Activity ◽  
Neck Squamous Cell Carcinoma ◽  
Radiosensitizing Effect

SummaryBackground. Resistance to radiation therapy poses a major clinical problem for patients suffering from head and neck squamous cell carcinoma (HNSCC). Transforming growth factor ß (TGF-ß) has emerged as a potential target. This study aimed to investigate the radiosensitizing effect of galunisertib, a small molecule TGF-ß receptor kinase I inhibitor, on HNSCC cells in vitro. Methods. Three HNSCC cell lines were treated with galunisertib alone, or in combination with radiation. Of those three cell lines, one has a known inactivating mutation of the TGF-ß pathway (Cal27), one has a TGF-ß pathway deficiency (FaDu) and one has no known alteration (SCC-25). The effect on metabolic activity was evaluated by a resazurin-based reduction assay. Cell migration was evaluated by wound-healing assay, clonogenic survival by colony formation assay and cell cycle by FACS analysis. Results. Galunisertib reduced metabolic activity in FaDu, increased in SCC-25 and had no effect on CAL27. Migration was significantly reduced by galunisertib in all three cell lines and showed additive effects in combination with radiation in CAL27 and SCC-25. Colony-forming capabilities were reduced in SCC-25 by galunisertib and also showed an additive effect with adjuvant radiation treatment. Cell cycle analysis showed a reduction of cells in G1 phase in response to galunisertib treatment. Conclusion. Our results indicate a potential antineoplastic effect of galunisertib in HNSCC with intact TGF-ß signaling in combination with radiation.

scholarly journals mTOR/EGFR/iNOS/MAP2K1/FGFR/TGFB1 Are Druggable Candidates for N-(2,4-Difluorophenyl)-2′,4′-Difluoro-4-Hydroxybiphenyl-3-Carboxamide (NSC765598), With Consequent Anticancer Implications

2021 ◽  
Vol 11 ◽  
Author(s):  
Bashir Lawal ◽  
Ching-Yu Lee ◽  
Ntlotlang Mokgautsi ◽  
Maryam Rachmawati Sumitra ◽  
Harshita Khedkar ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Squamous Cell ◽  
Protein Interactions ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Growth Factor Receptor ◽  
Anticancer Activities

BackgroundThe application of computational and multi-omics approaches has aided our understanding of carcinogenesis and the development of therapeutic strategies. NSC765598 is a novel small molecule derivative of salicylanilide. This study aims to investigate the ligand-protein interactions of NSC765598 with its potential targets and to evaluate its anticancer activities in vitro.MethodsWe used multi-computational tools and clinical databases, respectively, to identify the potential drug target for NSC765598 and analyze the genetic profile and prognostic relevance of the targets in multiple cancers. We evaluated the in vitro anticancer activities against the National Cancer Institute 60 (NCI60) human tumor cell lines and used molecular docking to study the ligand-protein interactions. Finally, we used the DTP-COMPARE algorithm to compare the NSC765598 anticancer fingerprints with NCI standard agents.ResultsWe identified mammalian target of rapamycin (mTOR)/epidermal growth factor receptor (EGFR)/inducible nitric oxide synthase (iNOS)/mitogen-activated protein 2 kinase 1 (MAP2K1)/fibroblast growth factor receptor (FGFR)/transforming growth factor-β1 (TGFB1) as potential targets for NSC765598. The targets were enriched in cancer-associated pathways, were overexpressed and were of prognostic relevance in multiple cancers. Among the identified targets, genetic alterations occurred most frequently in EGFR (7%), particularly in glioblastoma, esophageal squamous cell cancer, head and neck squamous cell cancer, and non–small-cell lung cancer, and were associated with poor prognoses and survival of patients, while other targets were less frequently altered. NSC765598 displayed selective antiproliferative and cytotoxic preferences for NSCLC (50% growth inhibition (GI50) = 1.12–3.95 µM; total growth inhibition (TGI) = 3.72–16.60 μM), leukemia (GI50 = 1.20–3.10 µM; TGI = 3.90–12.70 μM), melanoma (GI50 = 1.45–3.59 µM), and renal cancer (GI50 = 1.38–3.40 µM; TGI = 4.84–13.70 μM) cell lines, while panels of colon, breast, ovarian, prostate, and central nervous system (CNS) cancer cell lines were less sensitive to NSC765598. Interestingly, NSC765598 docked well into the binding cavity of the targets by conventional H-bonds, van der Waal forces, and a variety of π-interactions, with higher preferences for EGFR (ΔG = −11.0 kcal/mol), NOS2 (ΔG = −11.0 kcal/mol), and mTOR (ΔG = −8.8 kcal/mol). NSC765598 shares similar anti-cancer fingerprints with NCI standard agents displayed acceptable physicochemical values and met the criteria of drug-likeness.ConclusionNSC765598 displayed significant anticancer and potential multi-target properties, thus serve as a novel candidate worthy of further preclinical studies.

scholarly journals Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo

2015 ◽  
Vol 10 (4) ◽  
pp. 501-508 ◽  
Author(s):  
Natalie R. Young ◽  
Christian Soneru ◽  
Jing Liu ◽  
Tatyana A. Grushko ◽  
Ashley Hardeman ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Neck Cell

scholarly journals Effects of salinomycin and CGP37157 on head and neck squamous cell carcinoma cell lines in vitro

2015 ◽  
Vol 12 (3) ◽  
pp. 4455-4461 ◽  
Author(s):  
AGMAL SCHERZED ◽  
STEPHAN HACKENBERG ◽  
KATRIN FROELICH ◽  
KRISTEN RAK ◽  
CHRISTIAN GINZKEY ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Squamous Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

Phase I Trial of Retinoic Acid and cis-Platinum for Advanced Squamous Cell Cancer of the Head and Neck Based on Experimental Evidence of Drug Synergism

1998 ◽  
Vol 118 (5) ◽  
pp. 597-602
Author(s):  
Robert A. Weisman ◽  
Randolph Christen ◽  
Gerrit Los ◽  
Vicky Jones ◽  
Charles Kerber ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Phase I ◽  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Complete Response ◽  
High Dose ◽  
Neck Squamous Cell Cancer

OBJECTIVE: Cis-platinum and 13- cis-retinoic acid have received much attention in the treatment of head and neck squamous cell cancer. Even though they have different mechanisms of action, little information is available on their interaction. This paper reviews experimental evidence for retinoic acid- cis-platinum synergy and presents toxicity data from patients with stage IV head and neck squamous cell cancer participating in a phase I trial combining 13- cis-retinoic acid and cis-platinum. METHODS: Patients were given 13- cis-retinoic acid orally daily for 7 days before and daily during high-dose (150 mg/m 2 per week for 4 weeks) intraarterial cis-platinum treatment with concurrent radiation. Toxicity was scored with use of the cancer and leukemia group B scale. RESULTS: In the phase I clinical trial, 15 patients were treated to determine a maximum tolerated dosage for 13- cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity was dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 patient treated with 60 mg/day. There were no deaths caused by toxicity; 12 of the 15 patients received all four weekly doses and the remaining 3 received three doses. Of 10 patients with fully evaluable data, all achieved a complete response at the primary site and 9 had a complete response in the neck. One patient had persistent neck disease after chemoradiation, and this tumor was removed with neck dissection. CONCLUSIONS: 13- cis-retinoic acid and cis-platinum are strongly synergistic against head and neck squamous cell cancer in vitro. Pretreatment with retinoic acid results in stronger synergy than concurrent drug exposure alone. Preliminary clinical experience with combined retinoic acid and cis-platinum in a design that parallels the in vitro study indicates that toxicity is acceptable with 13- cis-retinoic acid dosages of 20 mg/day in a high-dose-intensity intraarterial chemoradiation regimen. (Otolaryngol Head Neck Surg 1998;118:597–602.)

scholarly journals Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck

2021 ◽  
Vol 11 ◽  
Author(s):  
Sebastian Zahnreich ◽  
Senayit Gebrekidan ◽  
Gabriele Multhoff ◽  
Peter Vaupel ◽  
Heinz Schmidberger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Oxygen Deprivation ◽  
Protein Levels ◽  
Ca Ix ◽  
Hnscc Cell

Abundance and signaling of the epidermal growth factor receptor (EGFR) and programmed cell death protein ligand 1 (PD-L1) in head and neck squamous cell carcinoma (HNSCC) are not only genetically determined but are also subject to the traits of the tumor microenvironment, which has hitherto not been clarified completely. We investigated the impact of hypoxia on the EGFR system and on PD-L1 in six HPV negative HNSCC cell lines in vitro and in FaDu xenografts in vivo. Protein levels of EGFR, AKT, pAKT, ERK1/2, pERK1/2, CA IX, cleaved PARP (apoptosis), LC3B (autophagy), and PD-L1 were quantified by western blot after oxygen deprivation or CoCl2, staurosporine, and erlotinib treatment. In FaDu xenograft tumors the expression of EGFR, CA IX andCD34 staining were analyzed. Reduced oxygen supply strongly downregulated EGFR protein levels and signaling in FaDu cells in vitro and in vivo, and a transient downregulation of EGFR signaling was found in three other HNSCC cell lines. PD-L1 was affected by oxygen deprivation in only one HNSCC cell line showing increased protein amounts. The results of this study indicate a significant impact of the traits of the tumor microenvironment on crucial molecular targets of cancer therapies with high clinical relevance for therapy resistance and response in HNSCC.

scholarly journals Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Erliang Guo ◽  
Xionghui Mao ◽  
Xueying Wang ◽  
Lunhua Guo ◽  
Changming An ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Binding Protein ◽  
Neck Squamous Cell Carcinoma ◽  
Alternatively Spliced

AbstractHead and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

scholarly journals The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 919 ◽  
Author(s):  
Femke Verhees ◽  
Dion Legemaate ◽  
Imke Demers ◽  
Robin Jacobs ◽  
Wisse Evert Haakma ◽  
...  
Keyword(s):  
Dna Damage ◽  
Head And Neck ◽  
Cell Lines ◽  
Dna Damage Response ◽  
Squamous Cell ◽  
Antiviral Agent ◽  
Mitotic Catastrophe ◽  
Damage Response ◽  
Hnscc Cell

Cidofovir (CDV) is an antiviral agent with antiproliferative properties. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative head and neck squamous cell carcinoma (HNSCC) cell lines and whether it is caused by a difference in response to DNA damage. Upon CDV treatment of HNSCC and normal oral keratinocyte cell lines, we carried out MTT analysis (cell viability), flow cytometry (cell cycle analysis), (immuno) fluorescence and western blotting (DNA double strand breaks, DNA damage response, apoptosis and mitotic catastrophe). The growth of the cell lines was inhibited by CDV treatment and resulted in γ-H2AX accumulation and upregulation of DNA repair proteins. CDV did not activate apoptosis but induced S- and G2/M phase arrest. Phospho-Aurora Kinase immunostaining showed a decrease in the amount of mitoses but an increase in aberrant mitoses suggesting mitotic catastrophe. In conclusion, CDV inhibits cell growth in HPV-positive and -negative HNSCC cell lines and was more profound in the HPV-positive cell lines. CDV treated cells show accumulation of DNA DSBs and DNA damage response activation, but apoptosis does not seem to occur. Rather our data indicate the occurrence of mitotic catastrophe.

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