Two naturally-occurring compounds have shown marked effects on the apoptotic machinery in chronic lymphocytic leukemia (CLL). They are Curcumin (the active ingredient in the spice turmeric) and Green Tea Extract, also known as epigallocatechin-3-gallate (or EGCG).
The Purpose of the study: Chronic lymphocytic leukemia (CLL) is incurable with current chemotherapy treatments. It has been found that curcumin, which is the active ingredient in the spice turmeric, inhibits tumor metastasis, invasion, and angiogenesis in tumor cell lines. Studies evaluated the effects of curcumin on the viability of primary CLL B cells and its ability to overcome stromal mediated protection.
Experimental Design: The in vitro effect of curcumin on primary CLL B cell was evaluated using fluorescence activated cell sorter analysis and Western blotting. For some experiments, CLL B cells were co-cultured with human stromal cells to evaluate the effects of curcumin on leukemia cells cultured in their micro-environment. Finally, the effect of curcumin in combination with the green tea extract epigallocatechin-3 gallate (EGCG) was evaluated.
Results: Curcumin induced apoptosis in CLL B cells in a dose-dependent (5-20 μmol/L) manner and inhibited constitutively active prosurvival pathways, including signal transducers and activators of transcription 3 (STAT3), AKT, and nuclear factor κB. When the curcumin was administered simultaneously with EGCG, antagonism was observed for most patient samples, however sequential administration of these agents led to substantial increases in CLL B-cell death and could overcome stromal protection.
Conclusions: Curcumin treatment was able to overcome stromal protection of CLL B cells on in vitro testing and to synergize with EGCG when administered in a sequential fashion. Additional evaluation of curcumin as a potential therapeutic agent for treatment of CLL seems warranted. Link to this study.
Further notes on this study- the antagonism effect mentioned above found that the combination of the two natural substances together didn’t work as well as predicted: or as phrased in the study “… simultaneous culture had a less than additive effect.” Furthermore “sequential (or one at a time) administration led to dramatically more leukemic cell death than simultaneous administration.” So not only did exposing the cancer cells to these substances one at a time matter, but the order that they exposed the cancer cells to the substances mattered as well. When the green tea was added first, followed by curcumin, it worked much better than if the cells were exposed to the curcumin first, then followed by the green tea.
It should also be noted that the study used curcumin that was not bio-available, and doing so probably would have enhanced the effectiveness of the overall treatment as noted in the final paragraphs of this study.
There are many bio-available forms of curcumin available on the market today. Please use this link to read more about them.
Studies in humans regarding CCL and epigallocatechin gallate (EGCG) which is the major component of green tea. Mayo first tested EGCG in a variety of laboratory assays about eight years ago (above study), and it was found to reduce the survival of CLL leukemic cells. This laboratory finding was followed by a successful phase I clinical trial — the first time green tea extract had been studied in CLL patients.
In this study researchers found that the blood lymphocyte (leukemia cell) count was reduced in one-third of participants, and that the majority of patients who entered the study with enlarged lymph nodes due to involvement by CLL saw a 50 percent or greater reduction in their lymph node size.
Dr Tait Shanafelt, hematologist and lead author of the study, said: “Although only a comparative phase III trial can determine whether EGCG can delay progression of CLL, the benefits we have seen in most CLL patients who use the chemical suggest that it has modest clinical activity and may be useful for stabilizing this form of leukemia, potentially slowing it down.”
“These studies advance the notion that a nutraceutical like EGCG can and should be studied as cancer preventives,” says Neil Kay, M.D., a hematology researcher whose laboratory first tested the green tea extract in leukemic blood cells from CLL patients. “Using nontoxic chemicals to push back cancer growth to delay the need for toxic therapies is a worthy goal in oncology research — particularly for forms of cancer initially managed by observation such as CLL.”
Mayo reports that many patients diagnosed with CLL have started to include EGCG supplements as part of their therapies. Supplements are readily available over the counter. Link to this study
More on CCL and green tea extract- Author and alternative cancer advocate Ralph Moss, PhD, reviewed a study in his newsletter, Cancer Decisions. According to Dr. Moss, 33 patients were treated with varying dosages of EGCG. The doses ranged from 400 mg up to 2,000 mg, twice a day. After just one month of treatment, one patient experienced a partial remission. A third of the patients experienced more than a 20 percent decrease in the number of lymphocytes in their blood. And 11 out of 12 patients that previously had visibly swollen lymph nodes experienced a reduction of at least 50 percent in the size of these nodes. Although the standardized form of EGCG that was used in the study is not available on the market there are several reputable companies that produce EGCG as a supplement.
The next study involved patients who began drinking green tea on their own and the observations that were made by doctors – This study is based on several patients who became aware of the effectiveness of green tea for leukemic conditions and began to use it on as a side treatments. One example, “This patient was categorized as having stage IV disease and observation was recommended. Follow-up CT scans in November 2003 (8 months after diagnosis) and May 2004 (14 months after diagnosis) demonstrated measurable progression of lymphadenopathy in the left axilla (largest node 3.0 cm× 2.3 cm) and mesentery (∼2.7 cm× 1.2 cm). The patient remained asymptomatic and continued observation was recommended. After hearing reports regarding the in vitro effects of green tea extract on CLL B-cells, the patient began drinking a cup of green tea each day (prepared with two tea bags) starting August 2004 (17 months after diagnosis). Follow-up CT scans in November 2004 (20 months after diagnosis) and June 2005 (27 months after diagnosis) demonstrated a >50% decrease in the sum of the products of the six largest lymph node areas consistent with a PR according to the International Working Group criteria for non-Hodgkins lymphoma. She continues to do well drinking green tea daily 27 months after diagnosis and has not required conventional therapy.” Read about four patients who employed green tea on their own to treat and stabilize their leukemic conditions without the need for further conventional intervention.
Two studies on green tea extract and prostate cancer- Asian cultures have promoted the many health benefits of green tea for thousands of years. In the last decade, hundreds of studies now confirm that you should be drinking a few cups of green tea every day. And two recent studies show that it provides particularly powerful prostate protection.
Study 1- A case-control study was conducted in Hangzhou, southeast China during 2001-2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases, and matched to the age of cases. Information on duration, quantity and frequency of usual tea consumption, as well as the number of new batches brewed per day, were collected by face-to-face interview using a structured questionnaire. The risk of prostate cancer for tea consumption was assessed using multivariate logistic regression adjusting for age, locality, education, income, body mass index, physical activity, alcohol consumption, tobacco smoking, total fat intake, marital status, age at marriage, number of children, history of vasectomy and family history of prostate cancer. Among the cases, 55.4% were tea drinkers compared to 79.9% for the controls. Almost all the tea consumed was green tea. The prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumption. The adjusted odds ratio (OR), relative to non-tea drinkers, were 0.28 (95% CI = 0.17-0.47) for tea drinking, 0.12 (95% CI = 0.06-0.26) for drinking tea over 40 years, 0.09 (95% CI = 0.04-0.21) for those consuming more than 1.5 kg of tea leaves yearly, and 0.27 (95% CI = 0.15-0.48) for those drinking more than 3 cups (1 litre) daily. The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer.
Study 2- Italian researchers studied 62 men with a pre-cancerous prostate condition, normally this would result in cancer in about 30 percent of cases. Half of the men were given a placebo and the other half consumed an extract of green tea daily. In the placebo group, 9 out of 30 men developed cancer. In the green tea group, however, only 1 out of 32 participants developed the disease. This is consistent with a study of Chinese men which found that those who consumed the most green tea were two-thirds less likely to develop prostate cancer.
Bio-available curcumin- in general curcumin is poorly absorbed from intestinal tract to bloodstream so it is important to use a bio-available formula which has 7 times the normal absorption rate over standard form curcumin. Link to more information on Curcumin