| Title |
EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin
|
|---|---|
| Published in |
Molecular and Cellular Biochemistry, September 2012
|
| DOI | 10.1007/s11010-012-1448-y |
| Pubmed ID | |
| Authors |
Sharmila Shankar, Luke Marsh, Rakesh K. Srivastava |
| Abstract |
Human pancreatic cancer is currently one of the fourth leading causes of cancer-related mortality with a 5-year survival rate of less than 5 %. Since pancreatic carcinoma is largely refractory to conventional therapies, there is a strong medical need for the development of novel and innovative cancer preventive strategies. The forkhead transcription factors of the O class (FOXO) play a major role in cell proliferation, angiogenesis, metastasis, and tumorigenesis. The objectives of this study were to examine whether FKHRL1/FOXO3a modulates antitumor activity of (-)-epigallocatechin-3-gallate (EGCG), an active ingredient in green tea, in pancreatic cancer model in vivo. PANC-1 cells were orthotopically implanted into Balb c nude mice and gavaged with EGCG after tumor formation. Cell proliferation and apoptosis were measured by Ki67 and TUNEL staining, respectively. The expression of PI3K, AKT, ERK, and FOXO3a/FKHRL1 and its target genes were measured by the western blot analysis and/or q-RT-PCR. FOXO-DNA binding was measured by gel shift assay. EGCG-treated mice showed significant inhibition in tumor growth which was associated with reduced phosphorylation of ERK, PI3K, AKT, and FKHRL1/FOXO3a, and modulation of FOXO target genes. EGCG induced apoptosis by upregulating Bim and activating caspase-3. EGCG modulated markers of cell cycle (p27/KIP1), angiogenesis (CD31, VEGF, IL-6, IL-8, SEMA3F, and HIF1α), and metastasis (MMP2 and MMP7). The inhibition of VEGF by EGCG was associated with suppression of neuropilin. EGCG inhibited epithelial-mesenchymal transition by upregulating the expression of E-cadherin and inhibiting the expression of N-cadherin and Zeb1. These data suggest that EGCG inhibits pancreatic cancer orthotopic tumor growth, angiogenesis, and metastasis which are associated with inhibition of PI3K/AKT and ERK pathways and activation of FKHRL1/FOXO3a. As a conclusion, EGCG can be used for the prevention and/or treatment of pancreatic cancer. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 69 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 13 | 19% |
| Student > Bachelor | 10 | 14% |
| Student > Master | 10 | 14% |
| Researcher | 7 | 10% |
| Student > Doctoral Student | 6 | 9% |
| Other | 7 | 10% |
| Unknown | 16 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 14 | 20% |
| Agricultural and Biological Sciences | 12 | 17% |
| Medicine and Dentistry | 11 | 16% |
| Chemistry | 3 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
| Other | 7 | 10% |
| Unknown | 20 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 September 2012.
All research outputs
#13,135,772
of 22,678,224 outputs
Outputs from Molecular and Cellular Biochemistry
#1,161
of 2,290 outputs
Outputs of similar age
#90,412
of 168,451 outputs
Outputs of similar age from Molecular and Cellular Biochemistry
#8
of 22 outputs
Altmetric has tracked 22,678,224 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,290 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
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We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.