anti-VEGF

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Nils,You pointed out that EGCG, a polyphenol from green tea, is a VEGF inhibitor and that this could be useful given the recent articles and press releases saying that VEGF is a major driving force behind polyp growth.Indeed, EGCG is an anti-VEGF, so is grape seed extract : Cancer Prev Res (Phila Pa). 2008 Dec;1(7):554-61.Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway.Wen W, Lu J, Zhang K, Chen S.Department

of Molecular Medicine, Beckman Research Institute of the City of Hope,

1500 East Duarte Road, Duarte, CA 91010, USA. wwen@...Blockade

of angiogenesis is an important approach for cancer treatment and

prevention. Vascular endothelial growth factor (VEGF) is one of the

most critical factors that induce angiogenesis and has thus become an

attractive target for antiangiogenesis treatment. However, most current

anti-VEGF agents often cause some side effects when given chronically.

Identification of naturally occurring VEGF inhibitors derived from diet

would be one alternative approach with an advantage of known safety.

Grape seed extract (GSE), a widely used dietary supplement, is known to

have antitumor activity. In this study, we have explored the activity

of GSE on VEGF receptor and angiogenesis. We found that GSE could

directly inhibit the kinase activity of purified VEGF receptor 2, a

novel activity of GSE that has not been characterized. GSE could also

inhibit the VEGF receptor/mitogen-activated protein kinase-mediated

signaling pathway in endothelial cells. As a result, GSE could inhibit

VEGF-induced endothelial cell proliferation and migration as well as

sprout formation from aorta ring. In vivo assay further showed that GSE

could inhibit tumor growth and tumor angiogenesis of MDA-MB-231 breast

cancer cells in mice. Consistent with the in vitro data, GSE treatment

of tumor-bearing mice led to concomitant reduction of blood vessel

density and phosphorylation of mitogen-activated protein kinase.

Depletion of polyphenol with polyvinylpyrrolidone abolished the

antiangiogenic activity of GSE, suggesting a water-soluble fraction of

polyphenol in GSE is responsible for the antiangiogenic activity. Taken

together, this study indicates that GSE is a well-tolerated and

inexpensive natural VEGF inhibitor and could potentially be useful in

cancer prevention or treatment.Gynecol Oncol. 2009 Jun;113(3):374-8. Epub 2009 Mar 25.Regulation of Vascular Endothelial Growth Factor in endometrial tumour cells by resveratrol and EGCG.Dann JM, Sykes PH, Mason DR, JJ.Laboratory

for Cell and Protein Regulation, Department of Obstetrics and

Gynaecology, University of Otago, Christchurch, New Zealand.

james.dann@...OBJECTIVE: Our

purpose was to establish whether resveratrol and

(-)-epigallocatechin-3-gallate (EGCG), two compounds extracted from

food, would reduce the amount of Vascular Endothelial Growth Factor

(VEGF) secreted into the supernatants of cultured endometrial cancer

cells. STUDY DESIGN: Endometrial cancer samples were collected from 19

consenting women who were undergoing hysterectomy operations to remove

tumours. Tumour cells were dispersed into single cell suspensions and

cultured. Two immortalised cell lines were also studied. After

incubating cells under various test and control conditions, ELISA was

used to measure VEGF levels in the supernatants. RESULTS: VEGF was

measurable at varied concentrations in the supernatants of cultured

cells, from both cell lines and primary cultures. Cobalt chloride

(CoCl(2)), a hypoxia mimic, increased the measured secretion of VEGF

from these cells. In contrast, treatment with either resveratrol or

EGCG significantly reduced secretion of VEGF. Further, resveratrol and

EGCG inhibited release from cells that were also exposed to CoCl(2).

CONCLUSION: Both resveratrol and EGCG induced significant reductions in

the amount of VEGF secreted into the supernatant of cultured

endometrial cancer cells. These results suggest that resveratrol and

EGCG may have the potential to inhibit angiogenesis in endometrial

tumours. Further investigation of these substances in endometrial

cancer is warranted.-----------------------Do note, however, that "grape seed extract" (not "grapefruit seed extract") is not a standardized term, so it just means that something inside grape in responsible for the anti-VEGF activity, but it does not say which compound(s) exactly. Resveratrol could be a possibility.So, there is an interesting idea that we might shrink polyps with, say, adding strong green tea or grape seed extract to irrigation.However, it turns out that EGCG is a COX-2 inhibitor, meaning that it has an effect that is close to that of aspirin (essentially a COX-1 inhibitor), but both reduce prostaglandin PGE2 in cells in some situations. We have a possibility that irrigating with EGCG might enhance inflammation. I say a possibility, because EGCG also has a parallel tendency to reduce the production of some leukotrienes, namely LTB4, and it also reduces 5-lipoxygenase. Given two parallel and diverging potential effects, we are hard pressed to say just from paper what effect EGCG or grape seed extract irrigation might have in vivo. The only to find out would be to try, but bearing in mind that :- it might be safer to begin with trying on the skin, especially if one has a skin prone to rashes and hives and therefore a sensitive one,- it might also be safer to try it on the inside rim of the nose first with, say, a q-tips dipped in the solution, the "best" (meaning : safest) trial situation being if one has a polyp protruding from the nose, which makes direct soaking with a q-tips a good experiment,- if used in irrigation while being infected, the tannins of green tea might have an undetermined effect on the germs, which will make it difficult to separate the anti-VEGF effect from the iron-sequestering action of the tannins ; in this case, it would be best to cure the infection first before attempting to determine the effect of green tea.Do note that I have not researched the potential general side effects of irrigating with green tea, so I cannot tell what may happen, except the above.In my opinion, green tea or grape seed extract could be tried safely on a q-tips in the case of polyps protruding. In the absence of interfering inflammation, a few days of soaking will tell if this strategy has merit. -----------------Rheumatol Int. 2009 Sep 24. [Epub ahead of print]Effects

of (-)-epigallocatechin-3-gallate on cyclooxygenase 2, PGE(2), and IL-8

expression induced by IL-1beta in human synovial fibroblasts.Huang GS, Tseng CY, Lee CH, Su SL, Lee HS.Department

of Radiology, Tri-Service General Hospital, National Defense Medical

Center, Taipei City 114, Taiwan, gsh5@....The

objective of this study was to examine the effects of

(-)-epigallocatechin-3-gallate (EGCG) on cyclooxygenase 2 (COX-2),

prostaglandin E(2) (PGE(2)), and interleukin 8 (IL-8) expression

induced by IL-1beta in human synovial fibroblasts. Cells were

enzymatically isolated from synovial tissue taken from patients

undergoing joint replacement surgery for osteoarthritis. Reverse

transcriptase-polymerase chain reaction, immunocytochemistry, and

western blotting were used to assess the COX-2 gene and protein

expression with the associated mechanisms. PGE(2) and IL-8 secretion

into the culture medium was assayed by enzyme-linked immunosorbent

assay. COX-2 upregulation in synovial fibroblasts induced by IL-1beta

was significantly suppressed by EGCG in a dose-dependent manner. PGE(2)

and IL-8 secretion was also induced by IL-1beta stimulation and

significantly suppressed by EGCG. The mechanism was associated with the

phosphorylation of IKKbeta. EGCG may inhibit the expression of

inflammatory mediators, such as COX-2, PGE(2), and IL-8, induced by

IL-1beta in human synovial fibroblasts. EGCG may be of value in the

treatment of synovial inflammation.In Vitro Cell Dev Biol Anim. 1996 Jun;32(6):340-4.Inhibitory effect of tea polyphenols on histamine and leukotriene B4 release from rat peritoneal exudate cells.Matsuo N, Yamada K, Yamashita K, Shoji K, Mori M, Sugano M.Department of Food Science and Technology, Kyushu University School of Agriculture, Fukuoka, Japan.The

effect of tea polyphenols on the release of chemical mediators,

histamine and leukotriene B4 (LTB4), from rat peritoneal exudate cells

(PEC) was studied. Among polyphenols, (-)-epigallocatechin gallate

(EGCG) most strongly inhibited the histamine release from the cells

stimulated with a calcium ionophore, A23187 or compound 48/80. Though

(+)-catechin © and (-)-epicatechin (EC) had no effect,

(-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) moderately

inhibited the histamine release. Similarly, EGCG, ECG, and EGC

inhibited LTB4 release from PEC, whereas C and EC were not effective.

The magnitude of the inhibitory effect on the release of these

mediators of tea polyphenols was in the order of EGCG > ECG >

EGC. These results indicated an important role of the triphenol

structure in the inhibitory activity. Therefore, the possible

antiallergic effect of tea polyphenols can be expected.Nutr Cancer. 2003;46(2):172-8.Effects

of green tea and high-fat diet on arachidonic acid metabolism and

aberrant crypt foci formation in an azoxymethane-induced colon

carcinogenesis mouse model.Ju J, Liu Y, Hong J, Huang MT, Conney AH, Yang CS.Graduate Program of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ 08854, USA.Excessive

fat consumption is a risk factor for colon carcinogenesis, and green

tea consumption may reduce the risk of colon and other cancers. The

current study was designed to investigate the effects of green tea and

a high-fat diet on arachidonic acid metabolism and aberrant crypt foci

formation in an azoxymethane (AOM)-induced colon carcinogenesis mouse

model. We also determined whether green tea consumption altered the

size of regional fat pads. CF-1 female mice were maintained on either a

high-fat (20% corn oil) or a low-fat (5% corn oil) diet. AOM was given

subcutaneous at a dose of 7.5 mg/kg body weight at 6 wk and then a dose

of 10 mg/kg at 7 wk of age. Two weeks after the second AOM injection,

0.6% green tea (6 mg tea solids/ml) was given as the drinking fluid and

continued for 10 wk until the experiment was terminated. In the

AOM-treated mice not receiving green tea, the high-fat diet

significantly enhanced colonic levels of 5-lipoxygenase, leukotriene A4

hydrolase, and leukotriene B4, but it did not significantly alter

prostaglandin E2 levels and aberrant crypt foci formation. In

AOM-treated mice on the high-fat diet, green tea significantly

decreased colonic levels of cytosolic phospholipase A2, 5-lipoxygenase,

and leukotriene B4; green tea treatment also decreased the number of

aberrant crypt foci (P < 0.05). The weights of parametrial and

retroperitoneal fat pads were increased by the high-fat diet and

decreased by green tea treatment. The current results indicate that

green tea consumption and dietary fat modulate 5-lipoxygenase-dependent

pathway of arachidonic acid metabolism during AOM-induced colon

carcinogenesis. Green tea inhibits ACF formation in mice on a high corn

oil diet, suggesting its possible inhibitory effect on colon

carcinogenesis in populations such as those in Western countries that

consume high amounts of fat.