Preferential inhibition by (−)-epigallocatechin-3-gallate of the cell surface NADH oxidase and growth of transformed cells in culture

Morré, D. James; Bridge, Andrew W.; Wu, Lei; Morré, Dorothy M.

doi:10.1016/s0006-2952(00)00426-3

Cited by 82 publications

(78 citation statements)

References 31 publications

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“…Cellular growth is inhibited approximately 50% with 5 M EGCg in the first system, whereas 100 M EGCg is needed to achieve the same inhibition of normal cell growth (16).…”

Section: Discussionmentioning

confidence: 99%

Anti- Trypanosoma cruzi Activity of Green Tea ( Camellia sinensis ) Catechins

Paveto

Güida

Esteva

et al. 2004

Antimicrob Agents Chemother

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The trypanocidal action of green tea catechins against two different developmental stages of Trypanosoma cruzi is reported for the first time. This activity was assayed with the nonproliferative bloodstream trypomastigote and with the intracellular replicative amastigote parasite forms. An ethyl acetate fraction from Camellia sinensis green tea leaves, which contains most of the polyphenolic compounds and the maximal trypanocidal activity, was obtained by fractionation of the aqueous extract with organic solvents. The active compounds present in this extract were further purified by LH-20 column chromatography and were identified by highperformance liquid chromatography analysis with a photo diode array detector and gas chromatography coupled to mass spectroscopy. The following flavan-3-ols derivatives, known as catechins, were identified: catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. The purified compounds lysed more than 50% of the parasites present in the blood of infected BALB/c mice at concentrations as low as 0.12 to 85 pM. The most active compounds were gallocatechin gallate and epigallocatechin gallate, with minimal bactericidal concentrations that inhibited 50% of isolates tested of 0.12 and 0.53 pM, respectively. The number of amastigotes in infected Vero cells decreased by 50% in the presence of each of these compounds at 100 nM. The effects of the catechins on the recombinant T. cruzi arginine kinase, a key enzyme in the energy metabolism of the parasite, were assayed. The activity of this enzyme was inhibited by about 50% by nanomolar concentrations of catechin gallate or gallocatechin gallate, whereas the other members of the group were less effective. On the basis of these results, we suggest that these compounds could be used to sterilize blood and, eventually, as therapeutic agents for Chagas' disease.Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in South and Central America (29). Human hosts are infected either by the triatomide insect vector bite, by blood transfusion, or by congenital transmission. The chronic phase of the disease occurs several years after infection, with cardiac and gastrointestinal pathologies being the typical clinical manifestations (6).The main approach to the elimination of Chagas' disease in areas of endemicity is the control of transmission by the insect vector (28). On the other hand, crystal violet is the only effective chemoprotective agent for banked blood. However, the high level of toxicity of this drug has imposed severe restrictions on its use (7,19,21,22).Treatment of patients with Chagas' disease relies on two chemotherapeutic agents: benznidazole and nifurtimox. These two drugs have several limitations because they are effective but highly toxic during the acute phase of the disease and scarcely beneficial in the chronic phase (23, 25). The undesirable side effects associated with these classical trypanocidal...

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“…Cellular growth is inhibited approximately 50% with 5 M EGCg in the first system, whereas 100 M EGCg is needed to achieve the same inhibition of normal cell growth (16).…”

Section: Discussionmentioning

confidence: 99%

Anti- Trypanosoma cruzi Activity of Green Tea ( Camellia sinensis ) Catechins

Paveto

Güida

Esteva

et al. 2004

Antimicrob Agents Chemother

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“…Evidence from laboratory studies with cancer cells in culture indicate that one 250 mg capsule of Capsol-T  every 4 h is equivalent to drinking l6 cups of green tea every 4 h. The need for l capsule of Capsol-T  every 4 h is predicated on pharmacokinetic information (Janle et al, 2008) and the knowledge that the inhibition of ENOX2 by Capsol-T  is reversible (Morré et al, 2000). In order to have therapeutic efficacy in selective killing of cancer cells, findings with cultured cancer cells show that the catechins must be present in the culture medium at a level of about 100 nM and to inhibit ENOX2 continuously at that level for a period of 48 to 72 h (Morré et al, 2000).…”

Section: Early Intervention Strategy Based On Green Tea-capsicum Synementioning

confidence: 99%

“…In order to have therapeutic efficacy in selective killing of cancer cells, findings with cultured cancer cells show that the catechins must be present in the culture medium at a level of about 100 nM and to inhibit ENOX2 continuously at that level for a period of 48 to 72 h (Morré et al, 2000). If EGCg, for example, is removed and replaced by EGCg-free media, even after 8 h, cancer cells in vivo resume normal rates of growth.…”

Section: Early Intervention Strategy Based On Green Tea-capsicum Synementioning

confidence: 99%

“…Tea catechins especially EGCg in combination with Capsicum have been characterized as specific ENOX2 inhibitors inducing apoptotic cell death in cancer but not in non-cancer cells (Morré et al, 2000;Chueh et al, 2004;Morré et al, 2009a). Safety and efficacy are well documented (Cooper et al, 2005).…”

Section: Early Intervention Strategy Based On Green Tea-capsicum Synementioning

confidence: 99%

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Early Detection: An Opportunity for Cancer Prevention Through Early Intervention

Morré¹,

Morré²

2012

Cancer Prevention - From Mechanisms to Translational Benefits

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“…tNOX (for tumor associated ECTO-NOX) is specific to the surfaces of cancer cells [7,9] . tNOX proteins are normally drug responsive and are inhibited by various anti tumor drugs and substances such as adriamycin [10] , the cancerfighting principal of green tea, (-)-epigallocatechin gallate (EGCg) [11] , capsaicin [9] , anti-tumor sulfonylureas [12] , cisplatinum, antitumor quassinoids, antitumor acetogenins [7] , the synthetic isoflavene phenoxodiol [13] and the anticancer principle from broccoli, sulforaphane (unpublished). The activity is normally resistant to inhibition by taxanes such as paclitaxel [14] .…”

Section: Introductionmentioning

confidence: 99%

tNOX (ENOX2) Target for Chemosensitization-Low-Dose Responses in the Hormetic Concentration Range

Morré¹,

Dick²,

Bosneaga³

et al. 2008

American J. of Pharmacology and Toxicology

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An emerging concept of cancer chemotherapy is that of chemosensitization. Most often applied to the treatment of drug-resistance cancers, chemosensitization has utility when such cancers are rendered drug sensitive through treatment with the sensitizing agent. A particularly striking example of chemosensitization is that encountered with the synthetic isoflavene phenoxodiol where patients with taxane-and/or platinum-resistant ovarian carcinoma once again become sensitive to these drugs following treatment with phenoxodiol. The latter appears to be a true chemosensitization in that the phenoxodiol need not be co-administered with the taxane or platinum drugs. Sensitivity is retained many weeks after the phenoxodiol has been cleared from the system. The response appears to be mediated through the primary drug target of phenoxodiol, a cancer-specific cell surface ECTO-NOX or ENOX protein designated tNOX (ENOX2). The ENOX protein family has been previously recognized as a hormetic target. The hypothesis under investigation is that chemosensitization and low dose synergies are most obvious in the hormetic range of concentrations and that the two phenomena, hormesis and chemosensitization, may be related mechanistically.

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Preferential inhibition by (−)-epigallocatechin-3-gallate of the cell surface NADH oxidase and growth of transformed cells in culture

Cited by 82 publications

References 31 publications

Anti- Trypanosoma cruzi Activity of Green Tea ( Camellia sinensis ) Catechins

Anti- Trypanosoma cruzi Activity of Green Tea ( Camellia sinensis ) Catechins

Early Detection: An Opportunity for Cancer Prevention Through Early Intervention

tNOX (ENOX2) Target for Chemosensitization-Low-Dose Responses in the Hormetic Concentration Range

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