Magnesium, Uric acid, Green tea, and CocoaJuly 2017
Green tea and the prevention of breast cancer: a case-control study in Southeast China.
Breast cancer is the most common malignancy in women worldwide. Tea has anticarcinogenic effects against breast cancer in experimental studies. However, epidemiologic evidence that tea protects against breast cancer has been inconsistent. A case-control study was conducted in Southeast China between 2004 and 2005. The incidence cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from breast disease clinics. Information on duration, frequency, quantity, preparation, type of tea consumption, diet and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Conditional logistic regression analyses were used to estimate odds ratios (ORs) and associated 95% confidence intervals. Compared with non-tea drinkers, green tea drinkers tended to reside in urban, have better education and have higher consumption of coffee, alcohol, soy, vegetables and fruits. After adjusting established and potential confounders, green tea consumption was associated with a reduced risk of breast cancer. The ORs were 0.87 (0.73-1.04) in women consuming 1-249 g of dried green tea leaves per annum, 0.68 (0.54-0.86) for 250-499 g per annum, 0.59 (0.45-0.77) for 500-749 g per annum and 0.61 (0.48-0.78) for >or=750 g per annum, with a statistically significant test for trend (P < 0.001). Similar dose-response relationships were observed for duration of drinking green tea, number of cups consumed and new batches prepared per day. We conclude that regular consumption of green tea can protect against breast cancer. More research to closely examine the relationship between tea consumption and breast cancer risk is warranted.
Carcinogenesis. 2007 May;28(5):1074-8
Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan.
Experimental studies suggest various features of anticancer activity of green tea including inhibitory effect of tumor invasion and metastasis. This study was conducted to examine the association between regular green tea consumption prior to diagnosis and subsequent risk of breast cancer recurrence. The Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) was started in 1988, in which information on lifestyle has routinely been collected from all first-visit outpatients by questionnaire. A total of 1160 new surgical cases of female invasive breast cancers with HERPACC information diagnosed between June 1990 and August 1998 were followed up through December 1999, and the risk (hazard ratio: HR) of recurrence was assessed with reference to daily green tea consumption using a Cox proportional hazard model. During 5,264 person-years of follow-up, 133 subjects (12%) were documented to suffer recurrence of breast cancer. A decreased HR for recurrence adjusted for stage was observed with consumption of three or more daily cups of green tea (HR=0.69, 95% confidence interval (95%CI)=0.47-1.00). Particularly in stage I, the HR was decreased statistically significantly (HR=0.43, 95%CI=0.22-0.84). A similar tendency was observed for stage II subjects, but was not present among more advanced stages. Although careful interpretation is needed, these results suggest the possibility that regular green tea consumption may be preventive against recurrence of breast cancer in early stage cases.
Cancer Lett. 2001 Jun 26;167(2):175-82
Modulation of MMP-2 and MMP-9 secretion by cytokines, inducers and inhibitors in human glioblastoma T-98G cells.
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)-a and interleukin (IL)-1b 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-a induced an up and down effect on MMP-2 and a slight induction of MMP-9. IL-1b 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.
Oncol Rep. 2017 Mar;37(3):1907-1913
Green Tea Polyphenol Induces Changes in Cancer-Related Factors in an Animal Model of Bladder Cancer.
Green tea polyphenol (GTP) suppresses carcinogenesis and aggressiveness in many types of malignancies including bladder cancer. However, the mechanistic basis of these effects is not well understood. This was investigated in the present study using a mouse model of chemically induced bladder cancer. C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14-24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation and microvessel density were evaluated along with immunohistochemical analysis of human antigen (Hu)R, vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. Nuclear HuR expression was not associated with any parameters such as carcinogenesis, muscle invasion, and GTP intake. These results indicate that GTP intake can suppress tumor progression and malignant behavior in an animal model of bladder cancer. We also speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer.
PLoS One. 2017 Jan 31;12(1):e0171091
Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3.
Green tea is one of the most commonly consumed natural health beverages in Taiwan’s market, with the major functional component catechin being shown to possess several biological activities such as antioxidation, anticancer, and prevention of cardiovascular disease. The objectives of this study were to develop a high-performance liquid chromatography-mass spectrometry method to determine the variety and content of catechins in green tea leaf waste, a by-product obtained during processing of tea beverage. In addition, catechin nanoemulsion was prepared to study its inhibition effect on prostate cancer cell PC-3. Results showed that a total of eight catechin standards were separated within 25 minutes by using a Gemini C18 column and a gradient mobile phase of 0.1% formic acid (A) and acetonitrile (B) with flow rate at 1 mL/min, column temperature at 30°C, and detection wavelength at 280 nm. Among various extraction solvents, 50% ethanol generated the highest yield of total catechins from tea leaf waste, of which five catechins were identified and quantified. The catechin nanoemulsion was composed of catechin extract, lecithin, Tween 80, and deionized water in an appropriate proportion, with the mean particle size being 11.45 nm, encapsulation efficiency 88.1%, and zeta potential -66.3 mV. A high stability of catechin nanoemulsion was shown over a storage period of 120 days at 4°C. Both catechin extract and nanoemulsion could inhibit growth of PC-3 tumor cells, with the half maximal inhibitory concentration being 15.4 µg/mL and 8.5 µg/mL, respectively. The PC-3 cell cycle was arrested at S phase through elevation of P27 expression and decline of cyclin A, cyclin B, cyclin-dependent kinase 2, and cyclin-dependent kinase 1 expression. In addition, both catechin extract and nanoemulsion could induce apoptosis of PC-3 cells through decrease in B-cell lymphoma 2 (bcl-2) expression and increase in cytochrome c expression for activation of caspase-3, caspase-8, and caspase-9. Taken together, both caspase-dependent and caspase-independent pathways may be involved in apoptosis of PC-3 cells.
Int J Nanomedicine. 2016 May 6;11:1907-26
Epigallocatechin-3-O-gallate up-regulates microRNA-let-7b expression by activating 67-kDa laminin receptor signaling in melanoma cells.
MicroRNAs (miRNAs) are non-coding RNAs involved in various biological processes by regulating their target genes. Green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) inhibits melanoma tumor growth by activating 67-kDa laminin receptor (67LR) signaling. To examine the effect of EGCG on miRNA expression in melanoma cells, we performed miRNA microarray analysis. We showed that EGCG up-regulated miRNA-let-7b expression through 67LR in melanoma cells. The EGCG-induced up-regulation of let-7b led to down-regulation of high mobility group A2 (HMGA2), a target gene related to tumor progression. 67LR-dependent cAMP/protein kinase A (PKA)/protein phosphatase 2A (PP2A) signaling pathway activation was involved in the up-regulation of let-7b expression induced by EGCG. These findings provide a basis for understanding the mechanism of miRNA regulation by EGCG.
Sci Rep. 2016 Jan 12;6:19225
Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction.
Amyloid-b (Ab)-induced mitochondrial dysfunction may play a role in the onset and progression of Alzheimer’s disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Plant-derived flavonoids have shown promise in improving certain AD phenotypes, but the overall mechanism of action(s) through which flavonoids protect from AD is still unknown. To identify flavonoids and other natural products that may correct amyloid-induced mitochondrial dysfunction, 25 natural products were screened for their ability to restore altered mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, or ATP levels in neuroblastoma cells expressing mutant amyloid-b protein precursor (AbPP). Epigallocatechin-3-gallate (EGCG) and luteolin were identified as the top two mitochondrial restorative compounds from the in vitro screen. EGCG was further tested in vivo to determine its effects on brain mitochondrial function in an AbPP/PS-1 (presenilin 1) double mutant transgenic mouse model of AD. EGCG treatment restored mitochondrial respiratory rates, MMP, ROS production, and ATP levels by 50 to 85% in mitochondria isolated from the hippocampus, cortex, and striatum. The results of this study lend further credence to the notion that EGCG and other flavonoids, such as luteolin, are ‘multipotent therapeutic agents’ that not only reduce toxic levels of brain Ab, but also hold the potential to protect neuronal mitochondrial function in AD.
J Alzheimers Dis. 2011;26(3):507-21