tannins and Carcinoma--Squamous-Cell

The present article reviewed the biological activities and possible dental application of three major polyphenols, i.e., lignin-carbohydrate complexes, tannins, and flavonoids, citing mostly our in vitro studies together with those from other groups. All these polyphenols showed much lower tumor-selective cytotoxicity against oral squamous cell carcinoma cells vs. normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast), in comparison to popular chemotherapeutic antitumor drugs. Several compounds showing higher tumor-selectivity did not induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in oral carcinoma cell lines. Lignin-carbohydrate complex protected the cells from the cytopathic effects of HIV infection and UV irradiation more efficiently than other polyphenols. Limited digestion of lignin-carbohydrate complex suggests that the lignin moiety is involved in the prominent anti-HIV activity, whereas the carbohydrate moiety may function in immunopotentiating activity through a cell surface receptor. Alkaline extract of plant leaf, which contains higher amounts of lignin-carbohydrate complex, showed potent anti-inflammatory action against IL-1β-stimulated human gingival fibroblasts. Local application of lignin-carbohydrate complex through oral mucosa is recommended, considering its poor intestinal absorption.

Topics: Adjuvants, Immunologic; Anti-HIV Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cytopathogenic Effect, Viral; DNA Fragmentation; Flavonoids; Gingivitis; HIV Infections; Humans; Lignin; Mouth Neoplasms; Nucleosomes; Polyphenols; Sunscreening Agents; Tannins; Ultraviolet Rays

The present study focuses on the antiproliferative activity of polyphenolic flavonoids found in defatted seeds of

Topics: Antioxidants; Azadirachta; Carcinoma, Squamous Cell; Flavonoids; Genes, Tumor Suppressor; Momordica charantia; Mouth Neoplasms; Plant Extracts; Quercetin; Rutin; Seeds; Tannins

Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in mice. In this study we investigated the anticancer mechanisms of PTF in human lung squamous carcinoma cells in vitro.. Human lung squamous carcinoma cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080) were tested. Cell viability was detected with MTT assay. Cell migration and invasion were assessed using a wound healing assay and a transwell chemotaxis chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric analysis. The levels of apoptosis-related and metastasis-related proteins were detected by Western blot and immunofluorescence.. PTF dose-dependently inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L, respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI-H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly inhibited cell migration, and reduced the number of invasive cells through Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK, but had no significant effect on the expression of ERK1/2 or JNK.. PTF induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells by decreasing MPPs expression through regulation of the MAPK pathway.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Survival; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Humans; Inhibitory Concentration 50; JNK Mitogen-Activated Protein Kinases; Lung Neoplasms; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Medicine, Tibetan Traditional; Mitogen-Activated Protein Kinases; Neoplasm Invasiveness; Phosphorylation; Tannins; Time Factors

Tannic acid (TA), is a potent anti-oxidant, showing anti-proliferative effects on numerous cancers. The ability of TA to induce proliferation inhibition on the rare tumor, gingival squamous cell carcinoma (GSCC), comprising <10% of all head and neck squamous cell carcinomas was studied in the YD-38 cell line. The main goal was to modulate the Jak2/STAT3 pathway using TA and to induce cell cycle arrest and apoptosis in GSCC. TA treatment induced G1 arrest and apoptosis in YD-38 cells. Molecular analysis revealed that TA inhibits Jak2/STAT3 pathway by preventing their expression as well as phosphorylation. This inhibition of STAT3 phosphorylation prevented the nuclear translocation and DNA binding capability of STAT3. Together with the inhibition of transcriptional regulatory function of STAT3, TA inhibited the expression of G1 phase modulators CDK-4, CDK-6, cyclin D1 and cyclin E. It is also evidenced that TA exerted an intense activation of p21Waf1/Cip1, p27Kip1 and p53 genes confirming its role in G1 phase inhibition. Additionally, upon treatment with TA, the expression of mitochondrial pore factors Bax, Bcl-2 and Bcl-XL were changed. We observed inhibition of Bcl-2 and an increase in mitochondrial localization of Bax leading to the loss of mitochondrial membrane potential, resulting in the release of cytochrome c to the cytosol. In addition, we perceived the activation of caspases upon TA treatment. Specific inhibition of caspase protected the cells from TA induced apoptosis. Taken together, this study reveals that TA significantly inhibits the Jak2/STAT3 signaling pathway and induces G1 arrest and mitochondrial apoptosis in YD-38 cells.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Gingival Neoplasms; Humans; Janus Kinase 2; Mitochondria; Phosphorylation; Signal Transduction; STAT3 Transcription Factor; Tannins

Hydrolyzable tannins showed higher cytotoxic activity against human oral squamous cell carcinoma and salivary gland tumor cell lines than against normal human gingival fibroblasts, whereas gallic acid, a component unit of tannins, showed much weaker selective cytotoxicity. The cytotoxic activity of dimeric compounds was generally higher than that of monomeric compounds. Macrocyclic ellagitannin oligomers, such as oenothein B, woodfordin C and woodfordin D showed the greatest cytotoxic activity, and their activity (per given number of molecules) was one order higher than those of gallic acid and epigallocatechin gallate, a major component of green tea. These compounds induced apoptotic cell death characterized by DNA fragmentation (as demonstrated by the TUNEL method) and cleavage of cytokeratin 18 by activated caspase(s) (as demonstrated by M30 monoclonal antibody). ESR spectroscopy revealed that these macrocyclic compounds at higher concentrations produced their own radicals and significantly enhanced the radical intensity of sodium ascorbate, possibly by their prooxidant actions. Catalase failed to eliminate their apoptosis-inducing activity, reducing the possibility of the involvement of hydrogen peroxide production in the extracellular fraction. These observations suggested that the antitumor activity of macrocyclic ellagitannin oligomers reported previously might be explained by their apoptosis-inducing activity.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Survival; Child; DNA Fragmentation; Female; Fibroblasts; Gingiva; Humans; Hydrolysis; In Situ Nick-End Labeling; Mouth Neoplasms; Plants, Medicinal; Salivary Gland Neoplasms; Structure-Activity Relationship; Tannins; Tumor Cells, Cultured

Alterations in tannic acid (TA) binding capacity of cell surface carbohydrates in normal, premalignant, and malignant squamous epithelium of the human uterine cervix have been studied using electron microscopic visualization in combination with microdensitometric evaluation. While in normal epithelium there is distinct binding in four to five cell layers of the deep intermediate zone, cells of carcinoma in situ and invasive cancer lesions lack TA binding. In moderate dysplasia an intermediate reacting pattern is found. Deep intermediate cells in areas bordering the carcinoma in situ lesions do not show any binding, although their ultrastructure cannot be distinguished from similar cells in normal tissue. The TA deposition within the deep intermediate zone is probably related to the presence here of glycoprotein-containing membrane-coating granules. The finding that TA binding discriminates between cells in normal squamous epithelium and morphologically normal cells in juxtaposition with lesional areas in premalignant and malignant epithelium opens the possibility for a more reliable cytologic diagnosis of cervical epithelial neoplasia.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Densitometry; Epithelium; Female; Humans; Hydrolyzable Tannins; Microscopy, Electron; Surface Properties; Tannins; Uterine Cervical Neoplasms

Drăgan's high-speed PBT (polychrome blue tannin) staining method enables cellular elements to be detected in oral smears in one minute at most. The basic dyes in the polychrome blue solution allow the acid-group-containing substrate to be detected in the nucleus, in the cytoplasm of epithelial cells and leukocytes, as well as in the elements of the flora. The chromatin shows a distinct basophilic, orthochromatic reaction. The fine, reddish-violet metachromatic granules in the cytoplasm are of a glycolipid nature and occur with the tonofibrils. The keratohyalin granules show a basophilic orthochromatic or metachromatic, homogeneous or granular reaction in relation to the chemically acid portions of their structure.

Topics: Carcinoma, Squamous Cell; Humans; Lip Neoplasms; Mouth Mucosa; Staining and Labeling; Tannins; Tongue Neoplasms; Trichomonas