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Green Tea and COX-2 Drugs Team to Curb Prostate Cancer
3/15/2007
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Positive outcome overlooks advantages of herbal COX-2 alternatives like turmeric and ginger
by Craig Weatherby


Inflammation fuels the growth of prostate and other cancers, and the body’s inflammation responses require intervention by an enzyme called COX-2.

The COX-2 enzyme is blocked by a fairly new class of analgesics known as COX-2 inhibitors. These include Vioxx and Bextra
both of which were withdrawn under pressure from the FDA due to increased heart risksand Celebrex (celecoxib), which remains on the market.

Researchers from the University of Wisconsin-Madison report that an antioxidant component of green tea called epigallocatechin-3-gallate (EGCG) slows the growth of prostate cancer in mice and in human cells.

And a new study shows that green tea works better when combined with low doses of celecoxib (Celebrex).

The EGCG in green tea seems to curb prostate cancer growth in three ways (Adhami VM et al 2004):
  • Modulates a molecular pathway driven by insulin-like growth factor-1 (IGF-1).
  • Inhibits an enzyme called 5-Lipoxygenase (5-LO), needed to produce an inflammatory messenger chemical called 5-HETE, without which prostate cancer cells cannot survive.
  • Impels cancer cells into programmed cell death (apoptosis).
COX-2 inhibitors like celecoxib also suppress prostate cancer in animals, but can cause adverse cardiovascular effects when taken in therapeutic doses over time.

The new study shows that green tea gives COX-2 inhibitors stronger cancer-fighting abilities at lower, safer doses.

According to lead author Hasan Mukhtar, Ph.D., “Celecoxib and green tea have a synergistic effect
each triggering cellular pathways that, combined, are more powerful than either agent alone. We hope that a clinical trial could lead to a preventative treatment as simple as tea time” (University of Wisconsin 2007).

What the research found

The Wisconsin team measured the effects of the two substances in cell cultures and in mice implanted with human prostate cancer cells (Adhami VM et al 2007).

Alone, both EGCG and celecoxib slowed human cancer-cell growth and limited the presence of known cancer-promoting proteinsprostate specific antigen or PSAwithin the cell samples.

But when the researchers combined EGCG and celecoxib, the pair suppressed cell growth by an additional 15 to 28 percent.

The researchers repeated the experiment in mice. In addition to slowed tumor growth, the mice that received a combination of green tea and celecoxib showed a greater decrease in prostate specific antigen (PSA) levels compared to that seen with celecoxib alone or green tea alone. (PSA levels are markers for detection and progression of prostate cancer.)

Alone, the celecoxib and green tea polyphenol significantly reduced the size of prostate tumors. But the decrease was even more dramatic when the two were used together. And combination reduced the levels of prostate specific antigen (PSA): the protein commonly used as a marker to detect and assess the progression of prostate cancer.

Compared with results of treatment with green tea or the COX-2 drug alone, the combination produced these enhanced effects:
  • Reduced cell growth
  • Increased apoptosis (cancer-cell suicide)
  • Lower levels of prostate-specific antigen
  • Lower levels of insulin-like growth factor-I levels
  • Lower levels of serum insulin-like growth factor binding protein-3.
As Dr. Mukhtar said in a University press release, “Prostate cancer typically arises from more than one defect in the cellular mechanics, which means that a single therapeutic might not work fighting a particular cancer long-term. If tests in human trials replicate these results, we could see a powerful combined therapy that is both simple to administer and relatively cost effective” (University of Wisconsin 2007).

Herbal alternatives to Celebrex?
It seems plausible to presume that natural COX-2 inhibitors like turmeric and ginger could prove to be powerful alternatives to synthetic COX-2 inhibitors like celecoxcib: substitutes that pose no risk of adverse cardiac effects and offer ancillary health benefits.

Curcumin
the anti-inflammatory, anti-cancer yellow pigment in turmericis a potent COX-2 inhibitor that halts the growth of prostate cancer cells in test tubes. (In mice, it also attacks the brain plaques associated with Alzheimer’s and turmeric alleviates arthritis pain in clinical trials.)

And among foods, ginger is the most potent inhibitor of another enzyme called 5-Lipoxygenase (5-LO), which helps produce an inflammatory messenger chemical called 5-HETE. Without 5-HETE, cancer cells in the prostate cannot survive more than a few hours.

Extra virgin olive oil also inhibits the 5-LO enzyme, thanks to its bounty of potent tyrosol-type antioxidants.

Given that inflammation drives most cancersnot just prostate tumorsthe lesson here is that it makes sense for men and women to drink green tea with ginger, use extra virgin olive oil, and enjoy turmeric and yellow curry to their heart’s content!


Sources
  • Adhami VM, Malik A, Zaman N, Sarfaraz S, Siddiqui IA, Syed DN, Afaq F, Pasha FS, Saleem M, Mukhtar H. Combined Inhibitory Effects of Green Tea Polyphenols and Selective Cyclooxygenase-2 Inhibitors on the Growth of Human Prostate Cancer Cells Both In vitro and In vivo. Clin Cancer Res. 2007 Mar 1;13(5):1611-9.
  • University of Wisconsin School of Medicine and Public Health. More Evidence Green Tea Helps Combat Prostate Cancer: Two Cups Daily with Common Painkiller Shown to Effectively Reduce Cancer Spread. March 1, 2007. Accessed online March 10, 2007 at http://www.med.wisc.edu/news/item.php?id=1948.
  • Adhami VM, Siddiqui IA, Ahmad N, Gupta S, Mukhtar H. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer. Cancer Res. 2004 Dec 1;64(23):8715-22.

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