Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epigallocatechin-3-gallate (EGCG), a major component in green tea polyphenols, has been proven to suppress colonic tumorigenesis in animal models and epidemiological studies. As EGCG is retained in the gastrointestinal tract after oral administration, this pharmacokinetics property gives it the potential to function as a chemopreventive agent against colon cancer. In this study, human colorectal carcinoma HT-29 cells were treated with EGCG to examine the anti-proliferative and pro-apoptotic effects of EGCG, as well as the molecular mechanism underlying these effects. Cell viability assay, nuclear staining, DNA fragmentation, caspase assay, cytochrome c release, DiOC6(3) staining, mitogen-activated protein kinases (MAPK) phosphorylation and trypan blue exclusion assays, were utilized to dissect the signaling pathways induced by EGCG. After 36 h treatment, EGCG inhibited HT-29 cell growth with an IC50 of approximately 100 microM. HT-29 cells treated with doses higher than 100 microM showed apparent nuclear condensation and fragmentation, which was confirmed by DNA laddering. Caspase-3 and -9 activation was detected after 12 h treatment, accompanied by mitochondrial transmembrane potential transition and cytochrome c release. Activation of MAPKs was detected as early signaling event elicited by EGCG. Inhibition of c-Jun N-terminal kinase (JNK) pathway showed the involvement of JNK in EGCG-induced cytochrome c release and cell death. EGCG-induced JNK activation was blocked by the antioxidants glutathione and N-acetyl-l-cysteine, suggesting that the cell death signaling was potentially triggered by oxidative stress. In summary, our results from this study suggest that in HT-29 human colon cancer cells (i) EGCG treatment causes damage to mitochondria, and (ii) JNK mediates EGCG-induced apoptotic cell death.
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PMID:Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells. 1281 84

Epigallocatechin-3-gallate (EGCG; molecular formula: C22H18011)is the most abundant catechin in green tea (Camellia sinensis Theaceae). Both EGCG and green tea have been shown to have cancer-preventive activity in a number of animal models, and numerous mechanisms have been proposed based on studies with human cell lines. EGCG has been shown to undergo extensive biotransformation to yield methylated and glucuronidated metabolites in mice, rats, and humans. In the present study, we determined the concentration-dependent uptake of EGCG by HT-29 human colon cancer cells (20-600 microM) and the dose dependence of EGCG plasma and tissue levels after a single dose of EGCG (50-2000 mg/kg i.g.) to male CF-1 mice. The cytosolic levels of EGCG were linear with respect to extracellular concentration of EGCG after treatment of HT-29 cells for 2 h (915.3-6851.6 microg/g). In vivo, EGCG exhibited a linear dose relationship in the plasma (0.03-4.17 microg/ml), prostate (0.01-0.91 microg/g), and liver (0.09-18.3 microg/g). In the small intestine and colon, however, the levels of EGCG plateaued between 500 and 2000 mg/kg i.g. These results suggest that absorption of EGCG from the small intestine is largely via passive diffusion; however, at high concentrations, the small intestinal and colonic tissues become saturated. The levels of 4''-O-methyl-EGCG and 4',4''-di-O-methyl-EGCG parallel those of EGCG with respect to dose. The present study provides information with respect to what concentrations of EGCG are achievable in mice and may guide dose selection for future cancer chemoprevention studies with EGCG.
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PMID:Dose-dependent levels of epigallocatechin-3-gallate in human colon cancer cells and mouse plasma and tissues. 1620 66

Antioxidants have been found to be quite successful in deterring certain disease processes for years, especially cancer. Antioxidants protect the body by neutralizing the free radicals and donating one of their own electrons, thus ending the scavenger reaction. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, is a valuable scavenger of reactive oxygen species in vitro as well as in vivo. Thymoquinone (TQ), a major active component of black seed (Nigella sativa), is also known for its powerful scavenger abilities as an inhibitor of oxidative stress and has been utilized in the Middle East for centuries for healing properties. These two potent antioxidants when compared to the chemotherapeutic drug of choice, 5-fluorouracil (5-FU), have demonstrated incredible chemotherapeutic responses to the SW-626 cell line. The objective of this study was to evaluate and compare the effects of SW-626 colon cancer cells after a 24, 48, and 72 hour incubation periods with low, medium, and high doses of EGCG, TQ, and 5-FU. Cell viability, cell number, cellular morphology, and cellular metabolism were compared for the control and treatment groups. The results of this study evidenced a similar significant decrease in cell number as early as 24 hours in the groups treated with TQ and EGCG compared to 5-FU. Increases in cellular damage were evident after 24, 48, and 72 hours and in all treated groups compared with the control. Reduced cell numbers in the treated groups suggests the possibility that TQ and EGCG may have similar chemotherapeutic effects on cancer cells as 5-FU.
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PMID:Comparison of potential chemotherapeutic agents, 5-fluoruracil, green tea, and thymoquinone on colon cancer cells. 1681 33

There have been no studies on specific tea polyphenol biomarkers and risk of colorectal cancer in humans. We prospectively examined the associations between validated biomarkers of specific tea polyphenols and risk of developing colorectal cancer among a cohort of 18,244 men in Shanghai, China, with 16 years of follow-up. Epigallocatechin (EGC), 4'-O-methyl-epigallocatechin (4'-MeEGC) and epicatechin, and their metabolites in baseline urine samples were measured on 162 incident colorectal cancer cases and 806 matched controls. Individuals with high prediagnostic urinary EGC levels had a lower risk of colon cancer. Compared with undetectable EGC, odds ratios (95% confidence interval) for colon cancer in the lowest, intermediate and highest tertile of detectable EGC were 0.64 (0.33-1.24), 0.60 (0.30-1.20) and 0.40 (0.19-0.83), respectively (p for trend = 0.02). A similar inverse relation between 4'-MeEGC and colon cancer also was observed. Compared with the lowest quartile, odds ratios (95% confidence intervals) for colon cancer in the 2nd, 3rd and 4th quartiles of urinary 4'-MeEGC were 0.49 (0.25-0.96), 0.32 (0.16-0.67) and 0.41 (0.20-0.84), respectively (p for trend = 0.006). The strongest protective effect was seen for regular tea drinkers who showed high levels of urinary EGC and 4'-MeEGC. No association between urinary levels of epicatechin or its metabolite and colon cancer risk was observed. Urinary levels of tea polyphenols and their metabolites were not associated with rectal cancer risk. The present study supports the notion of tea catechins as chemopreventive agents against the development of colon cancer in humans.
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PMID:Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai Cohort Study. 1714 97

While 5-fluorouracil continues to be the chemotherapeutic gold-standard for the treatment of colon cancer, the side effects of 5-FU are numerous due to its ability to attack both healthy and cancerous cells. However, research continues to provide positive findings in regards to antioxidants and their success in deterring certain disease processes, especially cancer. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, is a valuable scavenger of reactive oxygen species in vitro as well as in vivo. Thymoquinone (TQ), the major active component of Nigella sativa (black seed), is also known for its powerful scavenger abilities as an inhibitor of oxidative stress and has been utilized in the Middle East for centuries because of its capability to heal many different diseases. Therefore, the objective of this study was to investigate the role of sustained drug delivery of TQ, EGCG, and 5-FU on the metabolic activity as well as structural changes in the SW-626 human colon cancer cell line in culture. Results of this study indicate a sustained drug delivery of EGCG and TQ demonstrated significant (p < 0 .01) cellular destruction and interference of cellular metabolic functions of SW-626 human colon cancer cells, which was comparable to SW-626 cells exposed to sustained drug delivery of 5-FU. Furthermore, MDA, glutathione, and nitric oxide all revealed significant alterations (p<0.05) as early as 24 hours. Morphologically, cellular changes occurred after exposure to TQ and EGCG at 24 hours which were also comparable to cells exposed to 5-FU. The delivery of the natural agents may offer a safe alternative treatment in for colon cancer.
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PMID:A comparison of 5-fluorouracil and natural chemotherapeutic agents, EGCG and thymoquinone, delivered by sustained drug delivery on colon cancer cells. 1748 93