Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines

Abstract The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

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Tyrosine kinase profiling guides combined therapeutic strategies in head and neck cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.6078 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 6078-6078

Author(s):

R. Rodríguez-Barrueco ◽

M. Ortíz-Ruiz ◽

J. J. Cruz ◽

A. Ocana ◽

A. Pandiella

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cell Lines ◽

Neck Cancer ◽

Tyrosine Kinases ◽

Egf Receptor ◽

Drug Combinations ◽

Metastatic Setting

6078 Background: Squamous cell carcinoma of the head and neck (SCCHN) is still an incurable disease in the metastatic setting. A particular subgroup of proteins implicated in the head and neck cancer are the tyrosine kinases (TK). Therapeutic inhibition of several of them including the EGF receptor with cetuximab in combination with radiotherapy or chemotherapy has shown to be clinically useful. Beyond EGFR, oncogenic activation of other TKs may be implicated in the genesis/progression of SCCHN. In this context, the identification of the TKs activated in SCCHN is a must in order to adequately target these kinases with already available inhibitors. Methods: Here we have investigated activated tyrosine kinases in head and neck cancer tumors derived from patients using a human phospho protein array for 42 receptor tyrosine kinases (RTK). Western-blot experiments were performed to validate each phospho RTK in tumors from patients. The same approach was followed in a series of head and neck cancer cell lines. In vivo xenografted models were used to study the antiproliferative effect of the combination of specific TK inhibitors against them. Results: TK receptors of the EGF and the VEGF family were the mostly activated in tumors derived from patients. 90% of patients revealed high pEGFR content. In addition, other EGFR/HER family receptors, such as HER3, were also activated (phosphorylated) in samples from patients. These data were corroborated in the SCCHN cell lines. In these cells, other RTK signalling intermediates were also active. Particularly, the Akt and FAK kinases. Combination of the anti-EGFR-HER2 TK inhibitor lapatinib with dasatinib (that targets FAK) was synergistic in vitro. Combination of lapatinib with the anti-VEGFR TK inhibitor pazopanib was inefficient in vitro, but resulted in a better trend in response in the in vivo xenografted models, as compared to the action of the single agents. Conclusions: Rational target drug combinations should be based on the identification of activated TK receptors or downstream signalling molecules. In head and neck cancer combination strategies using anti-EGFR/HER, anti-FAK, and anti-VEGFR compounds increases the action of individual treatments. These results open the door for future clinical development of these drug combinations. No significant financial relationships to disclose.

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Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors

Journal of Medicinal Chemistry ◽

10.1021/jm990292i ◽

1999 ◽

Vol 42 (21) ◽

pp. 4434-4445 ◽

Cited By ~ 28

Author(s):

David Zacheis ◽

Arindam Dhar ◽

Shennan Lu ◽

Matora M. Madler ◽

Jozef Klucik ◽

...

Keyword(s):

Head And Neck Cancer ◽

Retinoic Acid ◽

Head And Neck ◽

Cell Lines ◽

Cancer Cell ◽

Neck Cancer ◽

Cancer Cell Lines ◽

Retinoic Acid Receptors

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In vitro chemosensitivity of head and neck cancer cell lines

European Journal of Medical Research ◽

10.1186/2047-783x-15-8-337 ◽

2010 ◽

Vol 15 (8) ◽

pp. 337 ◽

Cited By ~ 16

Author(s):

PJ Schuler ◽

S Trellakis ◽

J Greve ◽

M Bas ◽

C Bergmann ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cell Lines ◽

Cancer Cell ◽

Neck Cancer ◽

Cancer Cell Lines ◽

In Vitro Chemosensitivity

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Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells

Scientific Reports ◽

10.1038/s41598-021-98450-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Monica Benvenuto ◽

Sara Ciuffa ◽

Chiara Focaccetti ◽

Diego Sbardella ◽

Sara Fazi ◽

...

Keyword(s):

Head And Neck Cancer ◽

Salivary Gland ◽

Head And Neck ◽

Cell Lines ◽

Neck Cancer ◽

Immune Cells ◽

Proteasome Inhibition ◽

Erbb Receptors ◽

Human Tongue

AbstractHead and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signaling transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, protracted mice survival and adjusted tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. In addition, Bortezomib modified the expression of proteasome structural subunits in transplanted SALTO-5 cells. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.

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In�vitro measurement of glucose uptake after radiation and cetuximab treatment in head and neck cancer cell lines using 18F‑FDG, gamma spectrometry and PET/CT

Oncology Letters ◽

10.3892/ol.2019.10916 ◽

2019 ◽

Author(s):

Natasa Matic ◽

Marcus Ressner ◽

Emilia Wiechec ◽

Karin Roberg

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Glucose Uptake ◽

Cell Lines ◽

Cancer Cell ◽

Neck Cancer ◽

Gamma Spectrometry ◽

Pet Ct ◽

18F Fdg

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Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22179253 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9253

Author(s):

Jiraporn Kantapan ◽

Nathupakorn Dechsupa ◽

Damrongsak Tippanya ◽

Wannapha Nobnop ◽

Imjai Chitapanarux

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cell Lines ◽

Neck Cancer ◽

Critical Role ◽

Bioactive Compound ◽

Stem Cell Markers ◽

Cancer Stem Cell Markers ◽

Hnscc Cell

Cancer stem cells (CSCs) play a critical role in radiation resistance and recurrence. Thus, drugs targeting CSCs can be combined with radiotherapy to improve its antitumor efficacy. Here, we investigated whether a gallotannin extract from Bouea macrophylla seed (MPSE) and its main bioactive compound, pentagalloyl glucose (PGG), could suppress the stemness trait and further confer the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, we evaluate the effect of MPSE or PGG to suppress CSC-like phenotypes and radiosensitization of HNSCC cell lines using a series of in vitro experiments, tumorsphere formation assay, colony formation assay, apoptosis assay, and Western blotting analysis. We demonstrate that MPSE or PGG is able to suppress tumorsphere formation and decrease protein expression of cancer stem cell markers. MPSE or PGG also enhanced the radiosensitivity in HNSCC cells. Pretreatment of cells with MPSE or PGG increased IR-induced DNA damage (γ-H2Ax) and enhanced radiation-induced cell death. Notably, we observed that pretreatment with MPSE or PGG attenuated the IR-induced stemness-like properties characterized by tumorsphere formation and the CD44 CSC marker. Our findings describe a novel strategy for increasing therapeutic efficacy for head and neck cancer patients using the natural products MPSE and PGG.

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