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Zyflamend - Cox 2 Herbal Suppresses Prostate Cancer Growth

Posted: November 25, 2005 http://www.asco.org/images/clear.gifNEW YORK (Reuters Health) - An olive-oil based herbal extract preparation called Zyflamend suppresses the growth of prostate cancer cells and induces prostate cancer cells to self-destruct, according to a new study.

Zyflamend has the ability, in culture at least, to reduce prostate cancer cell growth by as much as 78 percent and induce cancer cell death or "apoptosis," scientists report in the journal Nutrition and Cancer.

"Together, these results suggest that Zyflamend might have some chemopreventive utility against prostate cancer in men," lead investigator Dr. Debra L. Bemis of Columbia University College of Physicians and Surgeons, New York told Reuters Health.

Zyflamend has both COX-1 and COX-2 anti-inflammatory effects, although its anti-cancer effects against prostate cancer are independent of COX-2 inhibition. COX inhibitors have shown value for prostate cancer patients, but data from recent trials of selective COX-2 inhibitors suggest that use of these drugs might have adverse effects on the heart.

Aspirin, a non-selective COX inhibitor, is not associated with these side effects and, instead, has well established benefits in people with heart disease. Zyflamend has a biochemical action profile similar to aspirin.

In the laboratory, Bemis and colleagues observed that treatment of prostate cancer cells with Zyflamend dramatically decreased COX-1 and COX-2 enzyme activity and attenuated cancer cell growth.

Bemis said "we are currently conducting a Phase I clinical trial for men with a pre-cancerous lesion of the prostate -- prostatic intraepithelial neoplasia -- to gain some information as to Zyflamend's potential to prevent or slow... progression to prostate cancer."

<dl class="AbstractPlusReport"><dt class="head">1: Nutr Cancer. 2007;57(1):78-87.<script language="JavaScript1.2"></script>Links
</dt><dd class="abstract"> Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.

Sandur SK, Ahn KS, Ichikawa H, Sethi G, Shishodia S, Newman RA, Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Zyflamend, a polyherbal preparation, was designed based on constituents that exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and apoptotic activities through a mechanism that is not well defined. Because the nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion, and metastasis of tumor cells, we postulated that Zyflamend modulates the activity of NF-kappa B. To test this hypothesis, we examined the effect of this preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that Zyflamend inhibited receptor activator of NF-kappa B ligand-induced osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B activation induced by both TNF and cigarette smoke condensate. The expression of NF-kappa B-regulated gene products involved in antiapoptosis (inhibitor-of-apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like interleukin-1betaconverting enzyme/caspase-8 inhibitory protein, TNF receptor-associated factor-1, and survivin) and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2, intercellular adhesion molecule, and matrix metalloproteinase-9) was also down-regulated by Zyflamend. This correlated with potentiation of cell death induced by TNF and chemotherapeutic agents. Overall, our results indicate that Zyflamend suppresses osteoclastogenesis, inhibits invasion, and potentiates cytotoxicity through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
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How It Works

Bottom Line: Laboratory studies suggest Zyflamend may have anti-inflammatory and anticancer activities. But clinical evidence is lacking.

Zyflamend is a herbal supplement consisting of Holy basil, turmeric, ginger, green tea, rosemary, hu zhang, Chinese goldthread, barberry, oregano, and scullcap. Promoters of Zyflamend claim that it has anti-inflammatory and antiaging effects. It has been shown in one laboratory study to reduce inflammation and cause cell death, but human data is lacking.
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<hr>Purported Uses

Cancer treatment
One laboratory showed that Zyflamend can reduce the number of prostate cancer cells in the laboratory. Data from clinical trials are lacking. Inflammation
A lab study showed that Zyflamend reduces inflammation but there are no data from clinical trials.
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<hr>Research Evidence

One laboratory study showed that Zyflamend reduced the number of prostate cancer cells by inactivating the COX-2 enzyme activity and by inducing cell death.
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<hr>Warnings

The FDA has recently issued a letter to an Internet distributor for exaggerated claims made for Zyflamend. Individuals taking Zyflamend should inform their physicians.
Women who are pregnant or nursing should consult their physicians before using Zyflamend.

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<hr>Do Not Take If

If you have hypersensitivity to any of the constituents.
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<hr>
Clinical Summary

Zyflamend is an herbal extract of ten different herbs (1). It is promoted as having anti-inflammatory and antiaging properties. Supporters claim that the beneficial effects of Zyflamend are due to the constituents, many of which reduce inflammation by decreasing cyclooxygenase-2 (COX-2) activity. In vitro studies showed that Zyflamend inhibits COX-1 and COX-2 enzymes, induces apoptosis (4), and inhibits proliferation (8) of human prostate cancer cells. Zyflamend is being investigated in a Phase I clinical trial involving men with prostatic intraepithelial neoplasia (PIN) (2) (7).

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<hr>Purported uses

Antiaging
Cancer treatment
Inflammation

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<hr>Constituents

Ocimum sanctum (Holy basil) leaf
Curcuma longa (Turmeric) rhizome
Zingiber officinale (Ginger) rhizome
Camellia sinensis (Green tea) leaf
Rosemarinus officinalis (Rosemary) leaf and essential oil
Polygonum cuspidatum (Hu Zhang) root
Coptis chinensis (Chinese goldthread) root
Berberis vulgaris (Barberry) root
Origanum heracleoticum (Oregano) leaf
Scutellaria baicalensis (Scullcap) root
(1)
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<hr>Mechanism of Action

Holy basil, turmeric, ginger, green tea, rosemary, hu zhang, Chinese gold thread and Scutellaria inhibit cyclooxygenase-2 activity and thereby reduce inflammation. In an in vitro study, Zyflamend reduced the proliferation of prostate cancer cells by inhibiting COX-2 activity and by inducing apoptosis (2). Zyflamend down-regulates NF-kappa B activiation (6). Zyflamend has been shown to inhibit Leukotriene B4 formation in an animal carcinogenesis model (5).

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<hr>Warnings

The FDA has recently issued a letter to an Internet distributor for exaggerated claims made for Zyflamend (3). Individuals using Zyflamend should be cautious of such claims.
Women who are pregnant or nursing should consult their physicians before using Zyflamend.
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<hr>Contraindications

Hypersensitivity to any of the constituents.
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<hr>Herb-Drug Interactions

The herbal constituents of Zyflamend can potentially interact with other drugs. Please check the individual herb listed above for more information.

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<hr>Literature Summary and Critique

Zyflamend is currently being studied in a Phase I clinical trial involving men with prostatic intraepithelial neoplasia (PIN).
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<hr>References

Product web site. http://www.new-chapter.com (accessed on August 1, 2008).
Capodice JL, et al. ZyflamendTM, a unique preparation inhibits arachidonic acid metabolism and suppresses prostate cancer cells, in vitro. Abstract presented at the 1st International Conference of the Society for Integrative Oncology, Nov 18, 2004.
Letter from the Food and Drug Administration. http://www.fda.gov/cder/warn/cyber/2005/CL122e.pdf (accessed on August 1, 2008).
Bemis DL, et al. Zyflamend, a unique herbal preparation with non selective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. Nutrition and Cancer 2005; 52(2): 202-12.
Yang P, Sun Z, Chan D, et al. Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model. Carcinogenesis. 2008 Nov;29(11):2182-9.
Sandur SK, Ahn KS, Ichikawa H, et al. Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products. Nutr Cancer. 2007;57(1):78-87.
Rafailov S, Cammack S, Stone BA, et al. The role of Zyflamend, an herbal anti-inflammatory, as a potential chemopreventive agent against prostate cancer: a case report. Integr Cancer Ther. 2007 Mar;6(1):74-6.
Yang P, Cartwright C, Chan D, et al. Zyflamend-mediated inhibition of human prostate cancer PC3 cell proliferation: effects on 12-LOX and Rb protein phosphorylation. Cancer Biol Ther. 2007 Feb;6(2):228-36.

<dl class="AbstractPlusReport"><dt class="head">Carnosol is a component of Rosemary, which is in Zyflamend mixture:

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</dt><dt class="head">1: Nutr Cancer. 2009;61(1):94-102.<script language="JavaScript1.2"></script>Links
</dt><dd class="abstract"> Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes associated with apoptosis in leukemic cells.

Zunino SJ, Storms DH.
United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, University of California, Davis 95616, USA. susan.zunino@ars.usda.gov
Carnosol, from the herb rosemary, has been shown to induce apoptotic cell death in high-risk pre-B acute lymphoblastic leukemia (ALL). In the present study, carnosol was tested for its ability to sensitize leukemia cells to chemotherapeutic agents. Carnosol reduced the percentage of cell death in the pre-B ALL lines SEM, RS4;11, and REH when combined with cytarabine, methotrexate, or vincristine compared to the chemotherapeutic agents alone. Analysis of DNA strand breaks by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that carnosol delayed DNA cleavage in the cells when combined with chemotherapeutic drugs. Co-treatment of the cells with carnosol and chemotherapeutic drugs did not reduce mitochondrial membrane depolarization compared to the drug treatment alone. Time course analysis of caspase-3 activation by flow cytometry showed co-treatment with carnosol and drugs increased the activation of caspase-3 above that observed for the chemotherapeutic drugs alone. A lower percentage of caspase-3 positive cells progressed to an apoptotic phenotype when co-treated with carnosol and the chemotherapeutic drugs compared to drugs alone. These data show that carnosol blocks the terminal apoptotic events induced by chemotherapeutic drugs and suggest that increased dietary intake of carnosol may potentially decrease the effectiveness of some standard chemotherapy treatments used for leukemia.
PMID: 19116879 [PubMed - indexed for MEDLIN
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