tretinoin and epigallocatechin-gallate

Cancer is considered a fetal disease caused by uncontrolled proliferation and progression of abnormal cells. The most efficient cancer therapies suppress tumor growth, prevent progression and metastasis, and are minimally toxic to normal cells. Natural compounds have shown a variety of chemo-protective effects alone or in combination with standard cancer therapies. Along with better understanding of the dynamic interactions between our immune system and cancer development, nutritional immunology-the use of natural compounds as immunomodulators in cancer patients-has begun to emerge. Cancer cells evolve strategies that target many aspects of the immune system to escape or even edit immune surveillance. Therefore, the immunesuppressive tumor microenvironment is a major obstacle in the development of cancer therapies. Because interaction between the tumor microenvironment and the immune system is a complex topic, this review focuses mainly on human clinical trials and animal studies, and it highlights specific immune cells and their cytokines that have been modulated by natural compounds, including carotenoids, curcumin, resveratrol, EGCG, and β-glucans. These natural compounds have shown promising immune-modulating effects, such as inhibiting myeloid-derived suppressor cells and enhancing natural killer and cytolytic T cells, in tumor-bearing animal models, but their efficacy in cancer patients remains to be determined.

Topics: Animals; beta-Glucans; Carotenoids; Catechin; Curcumin; Humans; Immune System; Immunologic Factors; Killer Cells, Natural; Mice; Neoplasms; Resveratrol; T-Lymphocytes; Tretinoin; Tumor Microenvironment

Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may be potentially applied in cell therapy or regenerative medicine as a new alternative source of stem cells. They could be particularly valuable in restoring cardiac tissue after myocardial infarction or other cardiovascular diseases. We investigated the potential of biologically active compounds, namely, angiotensin II, retinoic acid (RA), epigallocatechin-3-gallate (EGCG), vitamin C alone, and the combinations of RA, EGCG, and vitamin C with angiotensin II to induce cardiomyogenic differentiation of AF-MSCs. We observed that the upregulated expression of cardiac gene markers (NKX2-5, MYH6, TNNT2, and DES) and cardiac ion channel genes (sodium, calcium, the potassium) also the increased levels of Connexin 43 and Nkx2.5 proteins. Extracellular flux analysis, applied for the first time on AF-MSCs induced with biologically active compounds, revealed the switch in AF-MSCS energetic phenotype and enhanced utilization of oxidative phosphorylation for energy production. Moreover, we demonstrated changes in epigenetic marks associated with transcriptionally active (H3K4me3, H3K9ac, and H4hyperAc) or repressed (H3K27me3) chromatin. All in all, we demonstrated that explored biomolecules were able to induce alterations in AF-MSCs at the phenotypic, genetic, protein, metabolic, and epigenetic levels, leading to the formation of cardiomyocyte progenitors that may become functional heart cells in vitro or in vivo.

Topics: Adult; Amniotic Fluid; Angiotensin II; Ascorbic Acid; Calcium Channels; Cardiac Myosins; Catechin; Cell Differentiation; Connexin 43; Epigenesis, Genetic; Female; Histones; Homeobox Protein Nkx-2.5; Humans; Mesenchymal Stem Cells; Myocytes, Cardiac; Myosin Heavy Chains; Oxidative Phosphorylation; Potassium Channels; Pregnancy; Pregnancy Trimester, Second; Primary Cell Culture; Signal Transduction; Tretinoin; Troponin T

Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid leukemia (AML) in which the hybrid protein promyelocytic leukemia protein/retinoic acid receptor α (PML/RARα) acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid cell mutation. We aimed at explaining the molecular mechanism of green tea polyphenol epigallocatechin-3-gallate (EGCG) enhancement of ATRA-induced APL cell line differentiation. Tumor suppressor phosphatase and tensin homolog (PTEN) was found downregulated in NB4 cells and rescued by proteases inhibitor MG132. A significant increase of PTEN levels was found in NB4, HL-60 and THP-1 cells upon ATRA combined with EGCG treatment, paralleled by increased myeloid differentiation marker CD11b. EGCG in synergy with ATRA promote degradation of PML/RARα and restores PML expression, and increase the level of nuclear PTEN. Pretreatment of PTEN inhibitor SF1670 enhances the PI3K signaling pathway and represses NB4 cell differentiation. Moreover, the induction of PTEN attenuated the Akt phosphorylation levels, pretreatment of PI3K inhibitor LY294002 in NB4 cells, significantly augmented the cell differentiation and increased the expression of PTEN. These results therefore indicate that EGCG targets PML/RARα oncoprotein for degradation and potentiates differentiation of promyelocytic leukemia cells in combination with ATRA via PTEN.

Topics: Catechin; Cell Differentiation; Chromones; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; Leupeptins; Morpholines; Phenanthrenes; Promyelocytic Leukemia Protein; Proteolysis; PTEN Phosphohydrolase; Retinoic Acid Receptor alpha; Tretinoin

Acute myeloid leukemia and head and neck squamous cell carcinomas are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in tumor invasion and metastasis. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in the regulation of MMP-2 and MMP-9 in human immortalized fibroblasts from FA. Human FA immortalized fibroblast cell lines FA-A:PD220 and FA-D2:PD20 were grown in minimum essential medium (MEM) supplemented with 15% fetal bovine serum (FBS) and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed with phosphate‑buffered saline (PBS) and incubated in serum-free media with the following: phorbol 12-myristate 13-acetate (PMA) at 10-100 ng/ml; tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) at 0.1-25 ng/ml; lipopolysaccharide (LPS) at 10-100 µg/ml; epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10-100 µM without and with PMA; a nutrient mixture (NM) without and with PMA at 10-1,000 µg/ml; actinomycin-D and cyclohexamide at 2 and 4 µM; retinoic acid and dexamethasone at 50 µM. After 24 h, media were removed and analyzed for MMP-2 and MMP-9 by zymography. Both FA cell lines expressed only MMP-2 and responded similarly to cytokines, mitogens, inducers and inhibitors. PMA potently stimulated MMP-9 and had a moderate effect on MMP-2. TNF-α showed variable effects on MMP-2 and significantly enhanced MMP-9. IL-1β enhanced MMP-2 slightly and MMP-9 significantly. LPS had a moderate stimulatory effect on MMP-2 and no effect on MMP-9. EGCG, Dox and NM, without and with PMA, downregulated MMP-2 and MMP-9 expression. Actinomycin-D, retinoic acid and dexamethasone also had inhibitory effects on MMP-2. Our results showed that cytokines, mitogens and inhibitors modulated FA fibroblast MMP-2 and MMP-9 expression, suggesting the clinical use of MMP inhibitors, particularly such potent and non-toxic ones as the NM and its component EGCG in the management of FA cancers.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Antioxidants; Carcinogens; Catechin; Cattle; Cells, Cultured; Cytokines; Doxycycline; Enzyme Activators; Fanconi Anemia; Fibroblasts; Gene Expression Regulation, Enzymologic; Humans; Interleukin-1beta; Lipopolysaccharides; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Necrosis Factor-alpha

Brain tumors are highly aggressive, characterized by the secretion of high levels of matrix metalloproteinase (MMP)-2 and MMP-9 that degrade the extracellular matrix and basement membrane, allowing cancer cells to spread to distal organs. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activity. We investigated the roles of these in the regulation of MMP-2 and MMP-9 in human glioblastoma T-98G cells. Human T-98G cells were grown in DME supplemented with 15% fetal bovine serum and antibiotics in 24-well tissue culture plates. At near confluence, cells were washed with phosphate-buffered saline and incubated in serum-free media with: phorbol 12-myristate 13-acetate (PMA) at 10, 25, 50 and 100 ng/ml; tumor necrosis factor (TNF)-α and interleukin (IL)-1β at 0.1, 1, 10 and 25 ng/ml; lipopolysaccharide (LPS) at 10, 25, 50 and 100 µg/ml; epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10, 25, 50 and 100 µM without and with PMA; a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract without and with PMA at 10, 50, 100, 500 and 1,000 µg/ml; actinomycin D and cyclohexamide at 2 and 4 µM; retinoic acid and dexamethasone at 50 µM. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by zymography and densitometry. Glioblastoma T-98G cells expressed only one band corresponding to MMP-2. PMA treatment showed increased MMP-2 and MMP-9 secretions up to 25 ng/ml and decreased levels of secretions at 50 and 100 ng/ml, with no significant overall effect. TNF-α induced an up and down effect on MMP-2 and a slight induction of MMP-9. IL-1β demonstrated a slight dose-dependent increase in T-98G secretion of MMP-2, but no induction of MMP-9. LPS showed dose-dependent decreased inactive MMP-2 secretion, increased active MMP-2 secretion and no effect on MMP-9. EGCG, Dox and NM, without and with PMA, downregulated the expression of MMP-2 and MMP-9 in a dose-dependent manner. Actinomycin D, cyclohexamide, retinoic acid and dexamethasone also had inhibitory effects on MMP-2. Our results showed that cytokines, mitogens and inhibitors modulated T-98G cell MMP-2 and MMP-9 expression, suggesting the clinical use of MMP inhibitors, particularly such potent and non-toxic ones as the nutrient mixture and its component EGCG in the management of glioblastoma cancers.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Antioxidants; Carcinogens; Catechin; Cattle; Cytokines; Doxycycline; Enzyme Activators; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Interleukin-1beta; Lipopolysaccharides; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Molecules with synergistic effects often enhance the benefits of cancer therapy. We observed that the major catechin of green tea, (-)-Epigallocatechin-3-gallate (EGCG), induced retinoid X receptor-γ (RXRγ) expression in the SK-Ch-A1 cholangiocarcinoma cell line and in two colon carcinoma cell lines (LoVo and the derivative multi-drug resistant LoVoMDR). On this basis, we analyzed the effects of EGCG in combination with an RXRγ ligand, 6-OH-11-O-hydroxyphenantrene (IIF), or with a ligand of retinoic acid receptor, all-trans-retinoic acid (RA). IIF alone and in combination with EGCG activated the retinoic X response elements and induced the germ cell nuclear factor. In parallel, EGCG induced 67 kDa laminin receptor expression alone and in combination with IIF. We observed a synergistic growth inhibition with EGCG and IIF in combination at lower doses. These effects were accompanied by apoptosis activation through the mitochondrial pathway. Moreover, in LoVo cell line we observed an induction of Forkhead box O3 expression, another molecule involved in apoptosis activation. Finally, metalloproteinase activity and extracellular matrix metalloproteinase inducer (EMMPRIN) expression were inhibited and tumor cell invasion was strongly reduced in the SK-Ch-A1 cell line after treatment with EGCG and IIF. In conclusion, the use of specific RXR ligands in combination with catechins could open a new perspective in gastrointestinal tumor chemoprevention.

Topics: Apoptosis; Catechin; Cell Line, Tumor; Drug Synergism; Forkhead Box Protein O3; Gastrointestinal Neoplasms; Humans; Ligands; Metalloproteases; Mitochondria; Phenanthrenes; Retinoid X Receptor gamma; Tea; Tretinoin

The highly aggressive adult sarcomas are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9, which play crucial roles in tumor invasion and metastasis by degradation of the extracellular membrane leading to cancer cell spread to distal organs. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 secretion in chondrosarcoma (SW-1353), fibrosarcoma (HT-1080), liposarcoma (SW-872) and synovial sarcoma (SW-982) cell lines. The selected compounds included natural cytokines and growth factors, as well as chemical compounds applied in therapy of sarcoma and natural compounds that have demonstrated anticancer therapeutic potential. MMP-2 and MMP-9 secretions were analyzed by gelatinase zymography following 24-h exposure to the tested agents and quantitated by densitometry. Fibrosarcoma, chondrosarcoma, liposarcoma and synovial sarcoma showed bands corresponding to MMP-2 and MMP-9 with dose-dependent enhancement of MMP-9 with phorbol 12-myristate 13-acetate (PMA) treatment. In chondrosarcoma cells, tumor necrosis factor (TNF)-α had a stimulatory effect on MMP-9 and insignificant effect on MMP-2 and interleukin (IL)-1β stimulated MMP-9 and MMP-2. In fibrosarcoma and liposarcoma cells, TNF-α had a profound stimulatory effect on MMP-9, but no effect on MMP-2 and in synovial sarcoma an inhibitory effect on MMP-2 and no effect on MMP-9. IL-1β had a slight inhibitory effect on fibrosarcoma, liposarcoma and synovial sarcoma MMP-2 and MMP-9 except for MMP-9 in synovial sarcoma which showed slight stimulation. Lipopolysaccharide (LPS) stimulated expression of MMP-2 in fibrosarcoma and chondrosarcoma while inhibited it in liposarcoma. Doxycycline, epigallocatechin gallate and the nutrient mixture inhibited MMP-2 and MMP-9 in all cell lines. Actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone inhibited MMP-2 and -9 in chondrosarcoma and fibrosarcoma cells. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in adult sarcoma cell lines, suggesting these agents may be effective strategies to treat these cancers.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Carcinogens; Catechin; Cell Line, Tumor; Chondrosarcoma; Dactinomycin; Dexamethasone; Doxycycline; Fibrosarcoma; Humans; Interleukin-1beta; Lipopolysaccharides; Liposarcoma; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Sarcoma; Sarcoma, Synovial; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Necrosis Factor-alpha

Regular consumption of green tea benefits people in prevention from cardiovascular disorders, obesity as well as neurodegenerative diseases. (-)-Epigallocatechin-3-gallate (EGCG) is regarded as the most biologically active catechin in green tea. However, the stability and bioavailability of EGCG are restricted. The purpose of the present study was to investigate whether a pro-drug, a fully acetylated EGCG (pEGCG), could be more effective in neuroprotection in Parkinsonism mimic cellular model. Retinoic acid (RA)-differentiated neuroblastoma SH-SY5Y cells were pre-treated with different concentrations of EGCG and pEGCG for 30 min and followed by incubation of 25 microM 6-hydroxydopamine (6-OHDA) for 24h. We found that a broad dosage range of pEGCG (from 0.1 to 10 microM) could significantly reduce lactate dehydrogenase release. Likewise, 10 microM of pEGCG was effective in reducing caspase-3 activity, while EGCG at all concentrations tested in the model failed to attenuate caspase-3 activity induced by 6-OHDA. Furthermore, Western-blot analysis showed that Akt could be one of the specific signaling pathways stimulated by pEGCG in neuroprotection. It was demonstrated that 25 microM of 6-OHDA significantly suppressed the phosphorylation level of Akt. Only pEGCG at 10 microM markedly increased its phosphorylation level compared to 6-OHDA alone. Taken together, as pEGCG has higher stability and bioavailability for further investigation, it could be a potential neuroprotective agent and our current findings may offer certain clues for optimizing its application in future.

Topics: Caspase 3; Catechin; Cell Line, Tumor; Central Nervous System Agents; Dose-Response Relationship, Drug; Humans; L-Lactate Dehydrogenase; Neurons; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; Time Factors; Tretinoin

Acute promyelocytic leukaemia (APL) patients are successfully treated with all-trans retinoic acid (ATRA). However, concurrent chemotherapy is still necessary and less toxic therapeutic approaches are needed. Earlier studies suggested that in haematopoietic neoplasms, the green tea polyphenol epigallocatechin-3-gallate (EGCG) induces cell death without adversely affecting healthy cells. We aimed at deciphering the molecular mechanism of EGCG-induced cell death in acute myeloid leukaemia (AML). A significant increase of death-associated protein kinase 2 (DAPK2) levels was found in AML cells upon EGCG treatment paralleled by increased cell death that was significantly reduced upon silencing of DAPK2. Moreover, combined ATRA and EGCG treatment resulted in cooperative DAPK2 induction and potentiated differentiation. EGCG toxicity of primary AML blasts correlated with 67 kDa laminin receptor (67LR) expression. Pretreatment of AML cells with ATRA, causing downregulation of 67LR, rendered these cells resistant to EGCG-mediated cell death. In summary, it was found that (i) DAPK2 is essential for EGCG-induced cell death in AML cells, (ii) ATRA and EGCG cotreatment significantly boosted neutrophil differentiation, and 67LR expression correlates with susceptibility of AML cells to EGCG. We thus suggest that EGCG, by selectively targeting leukaemic cells, may improve differentiation therapies for APL and chemotherapy for other AML subtypes.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis Regulatory Proteins; Calcium-Calmodulin-Dependent Protein Kinases; Catechin; Cell Death; Cell Differentiation; Death-Associated Protein Kinases; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gene Knockdown Techniques; Humans; Leukemia, Myeloid, Acute; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Tretinoin; Tumor Cells, Cultured; Up-Regulation

To detect differentially expressed proteins in hepatocellular carcinoma cell line SMMC-7721 treated separately by eight telomerase inhibitors including antisense oligodeoxynuclectide of human telomerase RNA (hTR-ASODN), sense oligodeoxynuclectide of hTR (hTR-SODN), ASODN of human telomerase reverse transcriptase (hTERT-ASODN), SODN of hTERT (hTERT-SODN), epigallocatechin gallate (EGCG), 3'-azido-3'-deoxythymidine (AZT), all trans-retinoic acid (ATRA) and adriamycin (ADM) using surface enhanced laser desorption/ionization time of flight-mass spectrom (SELDI-TOF-MS) technology.. SELDI-TOF-MS technology and weak cation exchanger (WCX-2) protein chip were used to detect differentially expressed secretory and cytoplasmic proteins of SMMC-7721 cell treated separately by eight telomerase inhibitors. The control group was hepatocellular carcinoma SMMC-7721 cell without any disposal.. The results of WCX-2 protein chip showed that the secretory and cytoplasmic proteins were differentially expressed in SMMC-7721 cell treated separately by eight telomerase inhibitors. But some proteins were down-regulated or up-regulated together in all experimental groups. The molecular weight of these differential proteins were all less than 10,000 Da.. Differentially expressed and common changes of proteins in SMMC-7721 cell treated separately by eight telomerase inhibitors would associate with telomerase activity.

Topics: Carcinoma, Hepatocellular; Catechin; Cell Line, Tumor; Enzyme Inhibitors; Humans; Liver Neoplasms; Protein Array Analysis; Proteome; Telomerase; Tretinoin; Zidovudine

Transforming growth factor beta 1 (TGF-β1) is an inhibitor of muscle cell differentiation that is associated with fibrosis, poor regeneration and poor function in some diseases of muscle. When neutralizing antibodies to TGF-β1 or the angiotensin II inhibitor losartan were used to reduce TGF-β1 signaling, muscle morphology and function were restored in mouse models of Marfan Syndrome and muscular dystrophy. The goal of our studies was to identify additional agents that overcome the anti-myogenic effect of TGF-β1.. A high-content cell-based assay was developed in a 96-well plate format that detects the expression of myosin heavy chain (MHC) in C2C12 cells. The assay was used to quantify the dose-dependent responses of C2C12 cell differentiation to TGF-β1 and to the TGF-β1 Type 1 receptor kinase inhibitor, SB431542. Thirteen agents previously described as promoting C2C12 differentiation in the absence of TGF-β1 were screened in the presence of TGF-β1. Only all-trans retinoic acid and 9-cis retinoic acid allowed a maximal level of C2C12 cell differentiation in the presence of TGF-β1; the angiotensin-converting enzyme inhibitor captopril and 10 nM estrogen provided partial rescue. Vitamin D was a potent inhibitor of retinoic acid-induced myogenesis in the presence of TGF-β1. TGF-β1 inhibits myoblast differentiation through activation of Smad3; however, retinoic acid did not inhibit TGF-β1-induced activation of a Smad3-dependent reporter gene in C2C12 cells.. Retinoic acid alleviated the anti-myogenic effect of TGF-β1 by a Smad3-independent mechanism. With regard to the goal of improving muscle regeneration and function in individuals with muscle disease, the identification of retinoic acid is intriguing in that some retinoids are already approved for human therapy. However, retinoids also have well-described adverse effects. The quantitative, high-content assay will be useful to screen for less-toxic retinoids or combinations of agents that promote myoblast differentiation in the presence of TGF-β1.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Benzamides; Captopril; Catechin; Cell Differentiation; Cell Line; Cell Proliferation; Dioxoles; Dose-Response Relationship, Drug; Mice; Muscle Development; Myoblasts; Receptors, Transforming Growth Factor beta; Resveratrol; Signal Transduction; Smad3 Protein; Stilbenes; Transforming Growth Factor beta1; Tretinoin; Vitamin D; Vitamins

To investigate the combined effect of the major tea polyphenol, (-)-epigallocatechin gallate (EGCG) and retinoic acid (RA) on cervical adenocarcinoma.. Cell growth rate was examined after treatment for 4, 7 and 10 days with 0-100 microM EGCG and/or 1 microM RA in two cervical adenocarcinoma cell lines, HeLa and TMCC-1. The effect of EGCG treatment was examined for the induction of apoptosis by DNA ladder assay and caspase-3-related protease activity in cell lysate. Telomerase activity was detected by stretch PCR telomere extension assay. hTERT expression levels were quantified by a real-time PCR system.. Combining EGCG and RA increased the antiproliferative effect in adenocarcinoma cell lines, whereas EGCG or RA treatment alone caused a less sensitive response in these cells. Neither EGCG nor RA treatment alone affected apoptosis and telomerase activity. The combination treatment of EGCG and RA induced apoptosis and inhibited telomerase activity in adenocarcinoma cell lines. These results were consistent with those of an antiproliferative effect of EGCG and/or RA in cervical adenocarcinoma cells.. Our data suggest that EGCG and RA combined to prevent the carcinogenesis of cervical adenocarcinoma, induce apoptosis and inhibit telomerase activity. The treatments of combining EGCG and RA may be effective in preventing or treating cervical adenocarcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Caspase 3; Catechin; Cell Growth Processes; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Synergism; Female; HeLa Cells; Humans; Telomerase; Tretinoin; Uterine Cervical Neoplasms

Anti-oxidants have attracted a lot of interest on account of their function to protect the skin from oxidative stress by ultraviolet (UV) radiation.. This study examined the effects of epigallocatechin-3-gallate (EGCG), which is a green tea extract, on the extracellular matrix (ECM) changes induced by UV radiation and showed the comparative results with retinoic acid (RA).. The ECM metabolism is tightly controlled by the collagen degrading matrix metalloprotienases (MMPs) and their tissue inhibitors (TIMPs). Therefore, the expression of MMPs and TIMP-1 was investigated to evaluate the effects of EGCG and RA. Artificial skin was made using three-dimensionally cultured keratinocytes on a collagen matrix populated with fibroblasts. EGCG and RA were added into the medium of the fibroblasts and keratinocytes culture and also applied topically on artificial skins prior to UVA irradiation. The MMPs and TIMP-1 expression levels were measured using Western blot and a zymogram.. EGCG, like RA, decreased the level of MMPs production and increased TIMP-1 expression level. However, EGCG suppressed the activities of the gelatinases and augmented the expressions of the TIMP-1 more than RA did. RA decreased the MMP-1 and MMP-3 expression levels to a greater extent than EGCG. ECM alterations as a result of UVA appeared to be prevented more effectively using the EGCG treatment.. EGCG can reverse the ECM degradation induced by UV even with a topical application of a practical-use concentration. In particular, EGCG proved to be much more effective in ROS-related conditions, such as UVA exposure.

Topics: Antioxidants; Catechin; Cells, Cultured; Dermis; Epidermal Cells; Extracellular Matrix; Female; Fibroblasts; Humans; Keratinocytes; Keratolytic Agents; Matrix Metalloproteinases; Oxidative Stress; Tissue Inhibitor of Metalloproteinase-1; Tretinoin; Ultraviolet Rays