tannins and Lung-Neoplasms

Lung cancer is the leading cause of cancer-related death globally. Despite many advanced approaches to treat cancer, they are often ineffective due to resistance to classical anti-cancer drugs and distant metastases. Currently, alternative medicinal agents derived from plants are the major interest due to high bioavailability and fewer adverse effects. Tannins are polyphenolic compounds existing as specialized products in a wide variety of vegetables, fruits, and nuts. Many tannins have been found to possess protective properties, such as anti-inflammatory, anti-fibrotic, anti-microbial, anti-diabetic, and so on. This review aims to summarize the current knowledge addressing the anti-cancer effects of dietary tannins and their underlying molecular mechanisms. In vivo and in vitro studies provide evidences that anti-cancer effects of various tannins are predominantly mediated through negative regulation of transcription factors, growth factors, receptor kinases, and many oncogenic molecules. In addition, we also discussed the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of tannins, clinical trial results as well as our perspective on future research with tannins.

Topics: Diabetes Mellitus; Fruit; Humans; Lung Neoplasms; Plants; Tannins

Topics: Animals; Breast Neoplasms; Carcinogens, Environmental; Colonic Neoplasms; Diet; Dietary Fats; Esophageal Neoplasms; Humans; Liver Neoplasms; Lung Neoplasms; Mammary Neoplasms, Experimental; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Tannins; Urinary Bladder Neoplasms

Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis.. Cell lines were treated with CDDP, TA, and CDDP + TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the levels of ERS apoptosis pathway related genes were valuated by qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated.. The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP + TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest, and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher.. The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cisplatin; Humans; Lung Neoplasms; Mice; Mice, Nude; Tannins

The objective of the present study was to develop PTF-loaded solid lipid nanoparticles (PTF-SLNs) and investigate their efficacy in treating lung cancer. The PTF-SLNs were prepared by the thin film hydration method and verified by FTIR and TEM. Their physicochemical properties were characterized by particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), etc. Then, the pharmacodynamic studies of PTF-SLNs were performed on Lewis lung cancer cells and tumor-bearing mice. Finally, the safety studies were assessed by organ index, serum biochemical indicators, and histopathological changes. The PTF-SLNs were characterized by around 50 nm sphere nanoparticles, sustained ideal stability, and controlled drug release effects. The pharmacodynamic evaluation results showed that PTF-SLNs had stronger anti-tumor efficacy than PTF. An in vitro study revealed a more obvious cytotoxicity and apoptosis effect. The IC 50 values of PTF and PTF-SLNs were 67.43 μg/mL and 20.74 μg/mL, respectively. An in vivo study showed that the tumor inhibition rates of 2 g/kg PTF and 0.4 g/kg PTF-SLNs were 59.97% and 64.55%, respectively. The safety preliminary study indicated that PTF-SLNs improve the damage of PTF to normal organs to a certain extent. This study provides a nanoparticle delivery system with phenolic herbal extract to improve anti-tumor efficacy in lung cancer.

Topics: Animals; Drug Carriers; Lipids; Liposomes; Lung Neoplasms; Mice; Nanoparticles; Particle Size; Tannins

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects. However, whether TA can inhibit TGF-β1-mediated EMT in lung epithelial cells remains enigmatic. Both the human adenocarcinomic alveolar epithelial (A549) and normal bronchial epithelial (BEAS-2B) cells were treated with TGF-β1 with or without TA. Results showed that TA addition, markedly inhibited TGF-β1-induced EMT as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin, and vimentin. Furthermore, TA inhibited TGF-β1-induced cell proliferation through inducing cell cycle arrest at G0/G1 phase. TGF-β1-induced increase in the phosphorylation of Smad (Smad2 and 3), Akt as well as that of mitogen activated protein kinase (ERK1/2, JNK1/2, and p38) mediators was effectively inhibited by TA. On the other hand, TA reduced the TGF-β1-induced increase in TGF-β receptors expression. Using molecular docking approach, FTIR, HPLC and Western blot analyses, we further identified the direct binding of TA to TGF-β1. Finally, we conclude that TA might directly interact with TGF-β1, thereby repressing TGF-β signaling and subsequent EMT process in lung epithelial cells. Further animal studies are needed to clarify its potential therapeutic benefit in pulmonary fibrosis.

Topics: A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Biomarkers, Tumor; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Proliferation; Dose-Response Relationship, Drug; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Idiopathic Pulmonary Fibrosis; Intracellular Signaling Peptides and Proteins; Lung; Lung Neoplasms; Molecular Docking Simulation; Protein Binding; Signal Transduction; Tannins; Time Factors; Transforming Growth Factor beta1

In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.

Topics: Adenocarcinoma; Apoptosis; Caspases; Cell Survival; Dose-Response Relationship, Drug; Flavonoids; Humans; Lung Neoplasms; Mitochondria; Proto-Oncogene Proteins c-mdm2; Signal Transduction; Smilax; Tannins; Tumor Cells, Cultured; Tumor Suppressor Protein p53

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 inhibits the mutagenicity of several polycyclic aromatic hydrocarbons (PAHs) and their bay-region diol-epoxides. Our prior studies have shown that when applied topically to Sencar mice, tannic acid caused substantial inhibition of epidermal PAH metabolism, subsequent PAH-DNA adduct formation, and PAH-induced skin tumorigenesis (H. Mukhtar et al., Cancer Res., 48:2361-2365, 1988, and references therein). In this study the effects of tannic acid supplementation in the diet (1%, w/w, in AIN-76 diet) of Sencar mice on benzo(a)pyrene (BP) metabolism and its subsequent DNA binding and tumorigenesis in lung and forestomach were evaluated. Animals receiving a tannic acid-containing diet showed diminished aryl hydrocarbon hydroxylase and 7-ethoxy-resorufin O-deethylase activities in the forestomach and lung. Elevated glutathione S-transferase and NAD(P)H:quinone reductase activities were observed in these tissues. Maximum effects occurred after 45 days of feeding. Administration of [3H]BP p.o. to animals resulted in lower covalent binding to DNA in forestomach and lung of animals receiving tannic acid-containing diet as compared to animals receiving AIN-76 control diet. Tumor induction studies in forestomach and lung revealed significant protection against BP-induced tumorigenesis in animals fed tannic acid-supplemented diet as compared to animals fed control diet. The mice fed tannic acid-supplemented diet developed 3.3 forestomach tumors/mouse compared to 5.2 tumors/mouse in animals receiving control diet. The numbers of pulmonary tumors per mouse in animals fed tannic acid-supplemented diet and control diet were 1.6 and 3.1, respectively. Topical application of 7,12-dimethylbenz(a)anthracene to animals fed tannic acid-supplemented diet did not result in significant protection against skin tumorigenesis. However, a slight delay in the onset of skin tumor formation occurred in tannic acid-fed animals when compared to animals receiving control diet. Our data suggest that dietary supplementation with tannic acid affords protection against BP-induced forestomach and lung tumorigenesis in rodents.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Aryl Hydrocarbon Hydroxylases; Benzo(a)pyrene; Cytosol; Diet; DNA; DNA Adducts; Female; Gastric Mucosa; Hydrolyzable Tannins; Lung; Lung Neoplasms; Mice; Microsomes; Skin; Skin Neoplasms; Stomach; Stomach Neoplasms; Tannins

Topics: Adenocarcinoma; Breast Neoplasms; Colonic Neoplasms; Humans; Intestinal Neoplasms; Kidney Neoplasms; Lung Neoplasms; Microscopy, Electron; Molybdenum; Phosphorus; Rectal Neoplasms; Staining and Labeling; Tannins; Thyroid Neoplasms