Research Database

 

Author: Ram Prasad and Santosh K. Katiyar

Melanoma is the leading cause of skin cancer-related deaths. We have examined the effect of green tea polyphenols (GTPs), a natural mixture of epicatechin monomers, on melanoma cancer cell growth and the molecular mechanism underlying these effects using different human melanoma cell lines as an in vitromodel. Treatment of melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells. GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of melanoma cells. Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).

 

 

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Author: Ji Hoon Jung and Miyong Yun and Eun-Jeong Choo and Sun-Hee Kim and Myoung-Seuk Jeong and Deok-Beom Jung and Hyemin Lee and Eun-Ok Kim and Nobuo Kato and Bonglee Kim and Sanjay K. Srivastava and Kunihiro Kaihatsu and Sung-Hoon Kim

 

EGCG is a component of green tea known to have chemo-preventative effects on several cancers. However, EGCG has limited clinical application, which necessitates the development of a more effective EGCG prodrug as an anticancer agent. In the current study, EGCG derivatives were compared and evaluated for their stability and anti-tumour activity in human CML K562 and KBM5 cells. EGCG-MP showed most prolonged stability compared to other EGCG derivatives. EGCG-MP exerted significant cytotoxicity and increased apoptosis in K562 and KBM5 cells more effectively than the other EGCG derivatives. In addition, EGCG-MP dramatically induced SHP-1 leading to the decrease of BCR-ABL and STAT3 phosphorylation in CML cells, compared to treatment with EGCG. Furthermore, EGCG-MP reduced the phosphorylation of STAT3 and survival genes in K562 cells, compared to treatment with EGCG. Conversely, depletion of SHP-1 or application of the tyrosine phosphatase inhibitor pervanadate blocked the ability of EGCG-MP to suppress phosphorylation of BCR-ABL and STAT3, and the expression of survival genes downstream of STAT3. In addition, EGCG-MP treatment more effectively suppressed tumour growth in BALB/c athymic nude mice compared to the untreated control or EGCG-treated group. Consistently, immunohistochemistry revealed increased caspase 3 and SHP-1 activity and decreased phosphorylation of BCR-ABL in the EGCG-MP-treated group in the EGCG-treated group. Our findings demonstrate that EGCG-MP induces SHP-1-mediated inhibition of BCR-ABL and STAT3 signalling in vitro and in vivo more effectively than EGCG as a potent chemotherapeutic agent for CML treatment. 

 

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Author: Michael A. Moses and Ellen C. Henry and William A. Ricke and Thomas A. Gasiewicz

(−)-Epigallocatechin gallate (EGCG), a major tea polyphenol, elicits anticancer effects. However, the mechanism of action is not fully understood. Our laboratory previously showed that EGCG inhibits heat shock protein 90 (HSP90). We used nontumorigenic (NT), tumorigenic, and metastatic cancer cells from a novel human prostate cancer progression model to test the hypotheses that certain stages are more or less sensitive to EGCG and that sensitivity is related to HSP90 inhibition. Treatment of cells with EGCG, novobiocin, or 17-AAG resulted in more potent cytotoxic effects on tumorigenic and metastatic cells than NT cells. When tumorigenic or metastatic cells were grown in vivo, mice supplemented with 0.06% EGCG in drinking water developed significantly smaller tumors than untreated mice. Furthermore, EGCG prevented malignant transformation in vivo using the full prostate cancer model. To elucidate the mechanism of EGCG action, we performed binding assays with EGCG-Sepharose, a C-terminal HSP90 antibody, and HSP90 mutants. These experiments revealed that EGCG-Sepharose bound more HSP90 from metastatic cells compared with NT cells and binding occurred through the HSP90 C-terminus. In addition, EGCG bound HSP90 mutants that mimic both complexed and uncomplexed HSP90. Consistent with HSP90 inhibitory activity, EGCG, novobiocin, and 17-AAG induced changes in HSP90-client proteins in NT cells and larger differences in metastatic cells. These data suggest that EGCG may be efficacious for the treatment of prostate cancer because it preferentially targets cancer cells and inhibits a molecular chaperone supportive of the malignant phenotype. 

 

 

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Author: Binbin Chen and Guangyi Liu and Peimei Zou and Xing Li and Qiufa Hao and Bei Jiang and Xiangdong Yang and Zhao Hu

Cisplatin (CP)-induced nephrotoxicity hampers its application in clinic. Green tea, particularly its predominant polyphenolic constituent epigallocatechin-3-gallate (EGCG), possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the protective effects of EGCG against CP-induced nephrotoxicity in mice. Male C57/BL6 mice in different groups received single injection of CP (20 mg/kg) and EGCG (100 mg/kg) in various sets and kidney tissues and blood were collected after killing. Then, samples were used for biochemical and immunohistochemical assay. Our results showed EGCG decreased biochemical factors and immunohistochemical damage induced by CP. Besides, expression of phosphorylated-extracellular signal-regulated kinase (p-ERK), glucose-regulated protein 78 (GRP78), caspase-12, and apoptosis of kidney were decreased by EGCG via inhibition of endoplasmic reticulum (ER) stress-induced apoptosis.

 

 

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Author: Guang Hao and Wei Li and Koon Teo and Xingyu Wang and Jingang Yang and Yang Wang and Lisheng Liu and Salim Yusuf on behalf of INTERHEART China Study Investigators

 

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Author: Ming Chen and Lin Zhai and Maiken Cavling Arendrup

In this study, we investigate the susceptibility of Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, and Aspergillus fumigatus using the EUCAST microdilution minimum inhibitory concentration (MIC) method (final tea supernatant concentration range 5.0-0.005 mg/ml) to 23 different teas and tea catechins including epigallocatechin gallate (EGCG) isolated from green tea. All teas exhibited potent in vitro antifungal activity against C. glabrata. Six out of nine green teas and three of eight black teas had an MIC of 0.078 mg/ml, one white tea had an MIC of 0.156 mg/ml, and finally three of five oolong teas had an MIC of 0.156 mg/ml. Three teas exhibited activity against C. albicans (MIC 1.25 mg/ml), one green tea was active against C. parapsilosis (MIC 1.25 mg/ml), but none were effective against C. krusei, C. tropicalis or A. fumigatus at the concentrations tested. The MIC of EGCG was 0.3125 μg/ml against C. glabrata and 5.0 μg/ml against C. albicans and C. parapsilosis. The effect was fungicidal against C. glabrata at higher concentrations. In conclusion, EGCG and other yet undefined substances in tea have differential antifungal activity in vitro against C. glabrata, C. albicans and C. parapsilosis. These data indicate that components of tea and EGCG might be useful particularly for the treatment of C. glabrata infections and warrants further investigations.

 

 

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Author: Anja Mähler and Jochen Steiniger and Markus Bock and Lars Klug and Nadine Parreidt and Mario Lorenz and Benno F Zimmermann and Alexander Krannich and Friedemann Paul and Michael Boschmann

Background: Muscle weakness and fatigue are common symptoms in multiple sclerosis (MS). Green tea catechins such as (−)epigallocatechin-3-gallate (EGCG) are known to improve energy metabolism at rest and during exercise. Objective: We tested the hypothesis that EGCG improves energy metabolism and substrate utilization in patients with MS. Design: Eighteen patients (8 men) with relapsing-remitting MS (expanded disability status scale score <4.5, all receiving glatiramer acetate) participated in this randomized, double-blind, placebo-controlled, crossover trial at a clinical research center. All patients received EGCG (600 mg/d) and placebo over 12 wk (4-wk washout in between). After each intervention, fasting and postprandial energy expenditure (EE), as well as fat oxidation (FAOx) and carbohydrate oxidation (CHOx) rates, were measured either at rest or during 40 min of exercise (0.5 W/kg). At rest, blood samples and microdialysates from adipose tissue and skeletal muscle were also taken. Results: At rest, postprandial EE and CHOx, as well as adipose tissue perfusion and glucose supply, were significantly lower in men but higher in women receiving EGCG compared with placebo. During exercise, postprandial EE was lower after EGCG than after placebo, indicating an increased working efficiency (men > women). After placebo, exercise EE was mainly fueled by FAOx in both men and women. After EGCG, there was a shift to a higher and more stable CHOx during exercise in men but not in women. Conclusions: Our data indicate that EGCG given to patients with MS over 12 wk improves muscle metabolism during moderate exercise to a greater extent in men than in women, possibly because of sex-specific effects on autonomic and endocrine control. 

 

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Effects of dietary supplementation with green tea polyphenols on digestion and meat quality in lambs infected with Haemonchus contortus

Author: Zhong RZ and Li HY and Fang Y and Sun HX and Zhou DW

Ujumqin sheep are susceptible to infection by the gastrointestinal nematode Haemonchus contortus, which reduces productivity and total meat yield in sheep. Thus, the effects of green tea polyphenol (GTP) supplements (0, 2, 4, or 6 g of GTP/kg feed) on dietary nutrient digestibility and meat quality in lambs infected with H. contortus were examined; control lambs were not infected. H. contortusinfections did not affect digestion but the apparent digestibilities of nutrients were decreased by dietary 2 g of GTP/kg feed supplementation. There was an interaction between treatment and sampling time on plasma total protein, urea nitrogen, and amino acid concentrations. The antioxidant activity and meat color of INFGTP0 lambs decreased. In conclusion, H. contortus infections in lambs decreased meat quality, but appropriate levels of dietary GTP supplementation diminished these negative effects though lower dose of GTP supplement showed negative effects on digestion.

 

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Author: Hong Ro Kim and Rajesh Rajaiah and Qing-Li Wu and Shailesh R. Satpute and Ming T. Tan and James E. Simon and Brian M. Berman and Kamal D. Moudgil

Green tea, a product of the dried leaves of Camellia sinensis, is the most widely consumed beverage in the world. The polyphenolic compounds from green tea (PGT) possess antiinflammatory properties. We investigated whether PGT can afford protection against autoimmune arthritis and also examined the immunological basis of this effect using the rat adjuvant arthritis (AA) model of human rheumatoid arthritis (RA). AA can be induced in Lewis rats (RT.1l) by immunization with heat-killed Mycobacterium tuberculosis H37Ra (Mtb), and arthritic rats raise a T cell response to the mycobacterial heat-shock protein 65 (Bhsp65). Rats consumed green tea (2–12 g/L) in drinking water for 1–3 wk and then were injected with Mtb to induce disease. Thereafter, they were observed regularly and graded for signs of arthritis. Subgroups of these rats were killed at defined time points and their draining lymph node cells were harvested and tested for T cell proliferative and cytokine responses. Furthermore, the sera collected from these rats were tested for anti-Bhsp65 antibodies. Feeding 8 g/L PGT to Lewis rats for 9 d significantly reduced the severity of arthritis compared with the water-fed controls. Interestingly, PGT-fed rats had a lower concentration of the proinflammatory cytokine interleukin (IL)-17 but a greater concentration of the immunoregulatory cytokine IL-10 than controls. PGT feeding also suppressed the anti-Bhsp65 antibody response. Thus, green tea induced changes in arthritis-related immune responses. We suggest further systematic exploration of dietary supplementation with PGT as an adjunct nutritional strategy for the management of RA.

 

 

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