lignans and Head-and-Neck-Neoplasms

Despite the development of more advanced medical therapies, cancer management remains a problem. Head and neck squamous cell carcinoma (HNSCC) is a particularly challenging malignancy and requires more effective treatment strategies and a reduction in the debilitating morbidities associated with the therapies. Phytochemicals have long been used in ancient systems of medicine, and non-toxic phytochemicals are being considered as new options for the effective management of cancer. Here, we discuss the growth inhibitory and anti-cell migratory actions of proanthocyanidins from grape seeds (GSPs), polyphenols in green tea and honokiol, derived from the

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Carcinoma, Squamous Cell; Catechin; Cell Line, Tumor; Cell Movement; Cell Survival; Drug Evaluation, Preclinical; Head and Neck Neoplasms; Humans; Lignans; Magnolia; Polyphenols; Proanthocyanidins; Squamous Cell Carcinoma of Head and Neck; Tea; Vitis

The objective of the present study was to evaluate the action of the crude hydroalcoholic extract of Piper cubeba fruits and isolated lignans (cubebin, dihydrocubebin, ethylcubebin, hinokinin and methylcubebin) on head and neck cancer cells. We evaluated the influence of the Piper cubeba extract and isolated lignans (10, 50 e 100 μg/mL) for 4, 24, 48 and 72 h, in the larynx (Hep-2) and oral (SCC-25) squamous cell carcinoma cells and normal fibroblasts, on morphology, cell proliferation and migration, cytotoxicity, genotoxicity and gene and protein expression (PTGS2, PTGER3, PTGER4, MMP2, MMP9). The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Fibroblasts; Gene Expression; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Lignans; Molecular Targeted Therapy; Phytotherapy; Piper; Plant Extracts; Time Factors

Sesamin-treated human oral cancer cell lines FaDu, HSC-3, and Ca9-22 were subjected to a wound-healing assay. Furthermore, Western blotting was performed to assess the effect of sesamin on the expression levels of matrix metalloproteinase (MMP)-2 and proteins of the MAPK signaling pathway, including p-ERK1/2, P-p38, and p-JNK1/2. In addition, we investigated the association between MMP-2 expression and the MAPK pathway in sesamin-treated oral cancer cells. Sesamin inhibited cell migration and invasion in FaDu, Ca9-22, and HSC-3 cells and suppressed MMP-2 at noncytotoxic concentrations (0 to 40 μM). Furthermore, sesamin significantly reduced p38 MAPK and JNK phosphorylation in a dose-dependent manner in FaDu and HSC-3 cells.. These results indicate that sesamin suppresses the migration and invasion of HNSCC cells by regulating MMP-2 and is thus a potential antimetastatic agent for treating HNSCC.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Survival; Dioxoles; Head and Neck Neoplasms; Humans; Lignans; MAP Kinase Kinase 4; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Neoplasm Metastasis; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Squamous Cell Carcinoma of Head and Neck; Zanthoxylum

Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemoradiotherapy; Down-Regulation; Female; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Lignans; Mice, Nude; Radiation-Sensitizing Agents; Survivin; Tumor Burden; Xenograft Model Antitumor Assays

Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC-5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with the: (i) induction of apoptosis, (ii) correction of dysregulatory cell cycle proteins of G0/G1 phase. Honokiol decreased the expression levels of epidermal growth factor receptor (EGFR), mTOR and their downstream signaling molecules. Treatment of FaDu and SCC-1 cell lines with rapamycin, an inhibitor of mTOR pathway, also reduced cell viability of HNSCC cells. Administration of honokiol by oral gavage (100 mg/kg body weight) significantly (P < 0.01-0.001) inhibited the growth of SCC-1 and FaDu xenografts in athymic nude mice, which was associated with: (i) inhibition of tumor cell proliferation, (ii) induction of apoptosis, (iii) reduced expressions of cyclins and Cdks, and (iv) inhibition of EGFR signaling pathway. Molecular docking analysis of honokiol in EGFR binding site indicated that the chemotherapeutic effect of honokiol against HNSCC is mediated through its firm binding with EGFR, which is better than that of gefitinib, a commonly used drug for HNSCC treatment.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Binding Sites; Biphenyl Compounds; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Separation; Cell Survival; Dose-Response Relationship, Drug; ErbB Receptors; Female; Flow Cytometry; Head and Neck Neoplasms; Humans; Lignans; Magnolia; Mice; Mice, Nude; Molecular Docking Simulation; Phytotherapy; Plant Extracts; Signal Transduction; Sirolimus

This study aimed to investigate the utility of honokiol, a naturally occurring compound, in the treatment of head and neck squamous cell carcinoma (HNSCC) as well as its ability to target the epidermal growth factor receptor (EGFR), a critical therapeutic target in HNSCC, and to enhance the effects of other EGFR-targeting therapies.. Human HNSCC cell lines and the xenograft animal model of HNSCC were used to test the effects of honokiol treatment.. Honokiol was found to inhibit growth in human HNSCC cell lines, with 50% effective concentration (EC(50)) values ranging from 3.3 to 7.4 micromol/L, and to induce apoptosis, as shown through Annexin V staining. These effects were associated with inhibition of EGFR signaling, including downstream inhibition of mitogen-activated protein kinase, Akt, and signal transducer and activator of transcription 3 (STAT3), and expression of STAT3 target genes, Bcl-X(L) and cyclin D1. Furthermore, honokiol enhanced the growth inhibitory and anti-invasion activity of the EGFR-targeting agent erlotinib. Although HNSCC xenograft models did not show significant inhibition of in vivo tumor growth with honokiol treatment alone, the combination of honokiol plus cetuximab, a Food and Drug Administration-approved EGFR inhibitor for this malignancy, significantly enhanced growth inhibition. Finally, HNSCC cells rendered resistant to erlotinib retained sensitivity to the growth inhibitory effects of honokiol.. These results suggest that honokiol may be an effective therapeutic agent in HNSCC, in which it can augment the effects of EGFR inhibitors and overcome drug resistance.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biphenyl Compounds; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cetuximab; Dose-Response Relationship, Drug; Drug Synergism; Drugs, Chinese Herbal; ErbB Receptors; Erlotinib Hydrochloride; Head and Neck Neoplasms; Humans; Lignans; Mice; Mice, Nude; Quinazolines; Signal Transduction; Xenograft Model Antitumor Assays