Green tea (-)-epigalocatechin-3-gallate inhibits KIT activity and causes caspase-dependent cell death in gastrointestinal stromal tumor including imatinib-resistant cells.
Source
Division of Ultrafine Structure, Department of Pathology, Research Institute of International Medical Center of Japan, Tokyo, Japan.Abstract
Imatinib,
a selective tyrosine kinase inhibitor, has been used as a standard
first-line therapy for gastrointestinal stromal tumor (GIST) patients.
Unfortunately, most patients responding to imatinib will eventually
exhibit the resistance, the cause of which is not fully understood. The
serious clinical problems of imatinib-resistance demand alternative
treatment strategy. (-)-Epigallocatechin-3-gallate (EGCG), a main
component of green tea catechin, has been demonstrated potential
anti-tumor effects on various types of cancer cells. Here, we report for
the first time that EGCG has shown anti-tumor effects on
gastrointestinal stromal tumor cell line GIST-T1 by suppressing cell
proliferation and eventually inducing cell death via caspase-dependent
pathways. GIST-T1 and imatinib resistant GIST-T1 (GIST-T1 IR) cells were
used to assess the effects of EGCG. In both cell types, KIT activity
was completely inhibited after 4 h treatment with 60 muM EGCG. EGCG
specifically inhibited activated KIT, which was demonstrated by using
Ba/F3 cells transfected with human wild-type KIT construct. At a dose of
30 muM EGCG, the KIT activity remains but at more than 40 muM EGCG, the
KIT activity was abolished in these transfected-Ba/F3 cells. Our
results suggest that EGCG has a promising potential as a natural KIT
inhibitor and therefore it could be used as a novel therapeutic or
preventive reagent for GISTs including the imatinib-resistant cases.
Stomach cancer
Laboratory studies have found that green tea polyphenols inhibit the growth of stomach cancer cells in test tubes. The exposure of human stomach cancer KATO III cells to egcg led to both growth inhibition and the induction of programmed cell death (apoptosis) (Oncol Rep, 5(2):527-9 1998 Mar-Apr).
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DOSAGE
http://newsblog.mayoclinic.org/2010/06/04/green-tea-extract-appears-to-keep-cancer-in-check-in-majority-of-cll-patients/
The article that was published about this study is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727287/?tool=pubmed. The sentence defining the dosage states, “Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) was administered using the standard phase I design with three to six patients per dose level (range, 400 to 2,000 mg by mouth twice a day).” The article later suggests that people tolerated the maximum dose well and that some people who received the higher doses seemed to do better in some respects, which is probably why they used the highest dosage in the next study. Still, as someone with no expertise in this area, I wouldn’t try to dose myself based on this information, and I can see why the Mayo people don’t want to specify a dosage in the context of patients asking what they should take. I went to an integrative medicine specialist at a major cancer center, who recommended 1,000 mg. twice a day. I’m not sure whether a regular oncologist would necessarily know about this; some of them tend to be dismissive of anything other than meds as such.
EM says:
I was diagnosed with CLL about 6 months
ago. I am 52 years old, female and otherwise in really good health.
Since it is very early in the diagnosis with no symptoms (other than
some slightly enlarged lymph nodes), I have been in the watch and wait
phase. My internist (who discovered the CLL through a routine blood
test) prescribed a series of supplements included EGCG. I have been
taking AOR Active Green tea (700mg/455 catechins) twice a day. Along
with the EGCG I have also been taking Tumeric, Reservatrol, Vitamin D
and Omega-3 Fish oil twice a day. I just went back for my check several
weeks ago and the news was great! My WBC went down to 6800 from 11,500
and my LYMPH went down 51% from 61% and NEUT up to 36% from 31%! Yay! Of
course, we can’t be 100% sure that is all the supplements at work, but I
will take the good news nonetheless and continue with my course as is. I
have also read “Anti-Cancer – A New Way of Life” by David
Servan-Schrieber. Though at times it can be a bit technical, the
diet/mind/body portion of it is wonderfully written and I would highly
recommend it to read
