By Jane Byrne , 05-May-2010

Sulforaphane, a compound derived from broccoli and broccoli sprouts, could help prevent or treat breast cancer by inhibiting cancer stem cells (CSCs), found a new US study.

Researchers believe that eliminating the CSCs is key to controlling cancer and in findings published in Clinical Cancer Research they found that, in both mice and cell cultures, sulforaphane targeted and killed the cancer stem cells and prevented new tumours from growing.

Recent studies, report the authors, indicate that CSCs have the capacity to drive tumour resistance and relapse/recurrence of cancer, with evidence building for the theory that a variety of cancers are driven and sustained by a small proportion of CSCs.

According to the American Cancer Society, 94,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease.

The researchers argue that a lack of efficacy of current chemotherapies in advance and metastatic disease requires novel approaches to specifically target CSC populations.

The anticancer efficacy of sulforaphane, derived from broccoli/broccoli sprouts, has been evaluated in various cancers and the risk of premenopausal breast cancer was shown to be inversely associated with broccoli consumption, they added.

Furthermore, as a chemoprevention agent, sulforaphane possesses many advantages, such as high bioavailability and low toxicity. “Sulforaphane from broccoli extracts is efficiently and rapidly absorbed in the human small intestine and distributed throughout the body,” said the authors.

Clinical trials

These previous studies, said the researchers, provide a strong rationale for investigating the chemoprevention property of sulforaphane in clinical trials, and the authors said that its chemoprevention properties against cancer are through both ‘blocking’ and ‘suppressing’ effects.

The concentrations of sulforaphane used in the study were higher than what can be achieved by eating broccoli or broccoli sprouts, said the team, and they added that prior research suggests the concentrations needed to impact cancer can be absorbed by the body from the broccoli extract, but side effects are not known.

While the extract is available in capsule form as a supplement, concentrations are unregulated and will vary, claim the researchers.

And they revealed that they are currently developing a method to extract and preserve sulforaphane and that they will then be developing a clinical trial to test it for the prevention and treatment for breast cancer.

“This research suggests a potential new treatment that could be combined with other compounds to target breast cancer stem cells. Developing treatments that effectively target the cancer stem cell population is essential for improving outcomes,” says lead researcher Dr Max Wicha, distinguished professor of oncology and director of the U-M Comprehensive Cancer Center.

The study

The researchers said that they took mice with breast cancer and injected varying concentrations of sulforaphane from the broccoli extract, using used several established methods to assess the number of cancer stem cells in the tumours.

The authors explained that an Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro, while a nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumour growth upon cell reimplantation in secondary mice.

The potential mechanism was investigated using Western blotting analysis and β-catenin reporter assay, they added.

The researchers found that sulforaphane (1-5 μmol/L) decreased aldehyde dehydrogenase–positive cell population by 65 per cent to 80 per cent in human breast cancer cells and reduced the size and number of primary mammospheres by 8- to 125-fold and 45 per cent to 75 per cent, respectively.

Daily injection with 50 mg/kg sulforaphane for two weeks reduced aldehyde dehydrogenase–positive cells by >50 per cent in nonobese diabetic and severe combined immunodeficient xenograft tumours, they found.

And, the researchers added that sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumour growth after the reimplantation of primary tumour cells into the secondary mice, they added.

“Our study identified the down regulation of Wnt/β-catenin self-renewal pathway by sulforaphane as one of the possible mechanisms for its efficacy,” they concluded.

The researchers noted treatment with sulforaphane had little effect on the normal cells.

Source: Clinical Cancer Research
Published online ahead of print: doi: 10.1158/1078-0432.CCR-09-2937
Title: Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells
Authors: Y. Li, T. Zhang, H. Korkaya, S. Liu, H. Fang Lee, B. Newman, Y. Yu, S. G. Clouthier, S. J. Schwartz, M. S. Wicha, D. Sun

The traditional Chinese herb Scutellaria (called skullcaps in the West) contains a combination of plant chemicals that together can significantly slow the growth of several different cancers, according to a study published in the January 2009 issue of Planta Medica.

The authors say this herb might prove an important addition to current cancer treatments. “On the basis of our preliminary results, we expect maximum benefit from Scutellaria…in combination with standard therapy such as surgery, chemotherapy, and immunotherapy,” says Prahlad Parajuli, PhD, assistant professor in the Department of Neurosurgery at Wayne State University and Karmanos Cancer Institute in Detroit, Michigan.

Past studies have shown that Scutellaria has potent antibacterial, anti-inflammatory, and anti-cancer properties, which come primarily from natural plant chemicals (phytochemicals) called flavonoids. Most of the research conducted on Scutellaria so far has focused on the roots of the herb, which are rich in the flavonoid wogonin. However, the leaves and stems are also thought to be high in cancer-fighting phytochemicals, according to study co-author Nirmal Joshee, PhD, assistant professor of Plant Science at Fort Valley State University in Georgia.

To learn more about this herb and how it might combat cancer, the researchers analyzed leaf, stem, and root extracts from 13 different Scutellaria species. They found that each extract contained different combinations of six flavonoids: apigenin, baicalein, baicalin, chrysin, scutellarein, and wogonin. Most extracts contained three or four different flavonoids. Two extracts contained all six flavonoids.

They then treated human breast, prostate, and brain cancer cells, as well as non-cancerous cells, with the Scutellaria extracts. Nine of the extracts significantly halted the spread of cancer cells. The higher the dose and longer the duration of treatment, the more effectively the extracts killed cancer cells. Four extracts—all from the Scutellaria leaf—were particularly effective at triggering the death (apoptosis) of brain cancer cells.

The researchers also looked at how the flavonoids in Scutellaria—both individually and in combination—affected cancer cells. A combination of four flavonoids, each at a low dose, blocked the growth of brain cancer cells by almost 50 percent. However, when those same flavonoids were given individually at the same dose, they had no effect on the cancer, which suggests that each one possesses a different anti-cancer mechanism and the effects are amplified when the different flavonoids work together.

Future studies will help determine which combination, or combinations of phytochemicals have the greatest cancer-fighting ability. “Combining phytochemicals with synergistic anti-cancer activity would allow use of individual components at a very low dose, which would eliminate or reduce toxicity,” explains Dr. Parajuli.

Certain flavonoids in Scutellaria also appeared to target specific types of cancer. For example, baicalein significantly slowed the growth of brain cancer cells. This may be because individual flavonoids affect mechanisms that are unique to each cancer, the authors say.

Based on the promising results of studies done so far, the researchers say they may launch a human clinical study to investigate Scutellaria as an adjuvant cancer treatment within a few years.

Source:
Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK. In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Medica. 2009;75:41-48.

ScienceDaily (Feb. 23, 2010) — Bitter melon extract, a common dietary supplement, exerts a significant effect against breast cancer cell growth and may eventually become a chemopreventive agent against this form of cancer, according to results of a recent study.

“Our findings suggest that bitter melon extract modulates several signal transduction pathways, which induces breast cancer cell death,” said lead researcher Ratna B. Ray, Ph.D., professor in the Department of Pathology at Saint Louis University. “This extract can be utilized as a dietary supplement for the prevention of breast cancer.”

Results of this study are published in Cancer Research, a journal of the American Association for Cancer Research.

Previous research has shown Momordica charantia, also known as bitter melon, to have hypoglycemic and hypolipidemic effects, according to Ray. Because of these effects, the extract is commonly used in folk medicines as a remedy for diabetes in locales such as India, China and Central America, according to the researchers.

Using human breast cancer cells and primary human mammary epithelial cells in vitro, Ray and colleagues found the mechanism of bitter melon extract significantly decreased proliferation, that is, cell growth and division, and induced death in breast cancer cells. These early results offer an encouraging path for research into breast cancer.

“Breast cancer is a major killer among women around the world, and in that perspective, results from this study are quite significant,” said Rajesh Agarwal, Ph.D., professor in the Department of Pharmaceutical Sciences at the University of Colorado, Denver School of Pharmacy. “This study may provide us with one more agent as an extract that could be used against breast cancer if additional studies hold true.”

According to Agarwal, the Cancer Research associate editor for this study, the simple study design, clear-cut results and the overall importance of these findings in breast cancer prevention makes this research different from previous research.

However, he stressed that “this study is only a step towards establishing the cancer preventive efficacy of bitter melon against breast cancer.” Additional studies are needed to further understand the molecular targets of bitter melon extract in cancer cells, as well as for establishing its in vivo efficacy. Agarwal gave a note of caution, stating that while these results do provide hope as an anti-cancer agent, it is important to establish the validity of these results in animal models before adding them to one’s diet to inhibit breast cancer cell growth.

Ray and colleagues are currently conducting follow-up studies using a number of cancer cell lines to examine the anti-proliferative effect of the extract. They are also planning a preclinical trial to evaluate its chemopreventive efficacy by oral administration.

Bitter melon extract is cultivated in Asia, Africa and South America. Extract of this vegetable is being popularized as a dietary supplement in Western Countries, since it is known to contain additional glycosides such as mormordin, vitamin C, carotenoids, flavanoids and polyphenols.

American Association for Cancer Research (2010, February 23). Bitter melon extract decreased breast cancer cell growth. ScienceDaily. Retrieved March 1, 2010, from http://www.sciencedaily.com­ /releases/2010/02/100223131956.htm

ScienceDaily (Jan. 6, 2010) — Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.

Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.

“Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors,” said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.

Previous research has shown that pomegranate juice — punica granatum L — is high in antioxidant activity, which is generally attributed to the fruit’s high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.

Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.

After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth.

“We were surprised by our findings,” said Chen. “We previously found other fruits, such as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different.”

According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer.

“This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells,” said Stoner, who is not associated with this study. “It’s not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet.”

Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted.

Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner’s sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on estrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent.

“More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention,” Brown said. “This study does suggest that studies of the ellagitannins from pomegranates should be continued.”

Until then, Stoner said people “might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs.”

Adapted from materials provided by American Association for Cancer Research, via EurekAlert!, a service of AAAS.

ScienceDaily (Dec. 27, 2009) — A new study finds that the herb milk thistle may help treat liver inflammation in cancer patients who receive chemotherapy. Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the study indicates that the herb could allow patients to take potent doses of chemotherapy without damaging their liver.

Chemotherapy drugs frequently cause inflammation in the liver, and when they do, doctors must often lower patients’ doses or stop administering the therapies altogether. Clinical studies have investigated using milk thistle to treat liver damage from cirrhosis (from alcohol) or toxins (such as mushroom poisoning). Despite limited study data, the herb is often used for the treatment of chemotherapy associated liver problems. To test whether milk thistle could help treat chemotherapy associated liver problems, Kara Kelly, MD, of the New York-Presbyterian Hospital/Columbia University Medical Center’s Herbert Irving Comprehensive Cancer Center in New York City and colleagues conducted a randomized, controlled, double blind study in children with acute lymphoblastic leukemia (ALL), who commonly experience this side effect.

Fifty children with ALL were enrolled in the study and were randomized to receive milk thistle or placebo for 28 days. At the start of the study, all of the children had evidence of liver inflammation as measured by elevations in blood levels of the liver enzymes, aspartate amino transferase (AST) and amino alanine transferase (ALT). When the investigators performed liver function tests on the children at day 56 (28 days after receiving the herb or placebo), children receiving milk thistle had improvements in their liver enzymes compared with children receiving a placebo. Specifically, the group that took milk thistle had significantly lower levels of AST and a trend towards significantly lower levels of ALT. Taking milk thistle also seemed to help keep fewer patients from having to lower the dose of their medications: chemotherapy doses were reduced in 61 percent of the group receiving milk thistle, compared with 72 percent of the placebo group. In addition, milk thistle appeared to be safe for consumption.

The researchers also studied the effects of combining milk thistle with chemotherapy on leukemia cells grown in the laboratory. They found that milk thistle does not interfere with the cancer-fighting properties of chemotherapy.

“Milk thistle needs to be studied further, to see how effective it is for a longer course of treatment, and whether it works well in reducing liver inflammation in other types of cancers and with other types of chemotherapy,” said Dr. Kelly. “However, our results are promising as there are no substitute medications for treating liver toxicity.”

Ladas et al. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer, 2009; DOI: 10.1002/cncr.24723

ScienceDaily (Dec. 8, 2009) — A new study finds that compounds derived from the spices turmeric and pepper could help prevent breast cancer by limiting the growth of stem cells, the small number of cells that fuel a tumor’s growth.

Researchers at the University of Michigan Comprehensive Cancer Center have found that when the dietary compounds curcumin, which is derived from the Indian spice turmeric, and piperine, derived from black peppers, were applied to breast cells in culture, they decreased the number of stem cells while having no effect on normal differentiated cells.

“If we can limit the number of stem cells, we can limit the number of cells with potential to form tumors,” says lead author Madhuri Kakarala, M.D., Ph.D., R.D., clinical lecturer in internal medicine at the U-M Medical School and a research investigator at the VA Ann Arbor Healthcare System.

Cancer stem cells are the small number of cells within a tumor that fuel the tumor’s growth. Current chemotherapies do not work against these cells, which is why cancer recurs and spreads. Researchers believe that eliminating the cancer stem cells is key to controlling cancer. In addition, decreasing the number of normal stem cells — unspecialized cells that can give rise to any type of cell in that organ — can decrease the risk of cancer.

In this study, a solution of curcumin and piperine was applied to the cell cultures at the equivalent of about 20 times the potency of what could be consumed through diet. The compounds are available at this potency in a capsule form that could be taken by mouth.

The researchers applied a series of tests to the cells, looking at markers for breast stem cells and the effects of curcumin and piperine, both alone and combined, on the stem cell levels. They found that piperine enhanced the effects of curcumin, and that the compounds interrupted the self-renewal process that is the hallmark of cancer-initiating stem cells. At the same time, the compounds had no affect on cell differentiation, which is the normal process of cell development.

“This shows that these compounds are not toxic to normal breast tissue,” Kakarala says. “Women at high risk of breast cancer right now can choose to take the drugs tamoxifen or raloxifene for prevention, but most women won’t take these drugs because there is too much toxicity. The concept that dietary compounds can help is attractive, and curcumin and piperine appear to have very low toxicity.”

Curcumin and piperine have been explored by other researchers as a potential cancer treatment. But this paper, published online in the journal Breast Cancer Research and Treatment, is the first to suggest these dietary compounds could prevent cancer by targeting stem cells.

In addition, tamoxifen or raloxifene are designed to affect estrogen, which is a factor in most, but not all breast cancers. In fact, the aggressive tumors that tend to occur more often in women with a family history or genetic susceptibility are typically not affected by estrogen. Because curcumin and piperine limit the self renewal of stem cells, they would impact cancers that are not estrogen sensitive as well as those that are.

Researchers are planning an initial Phase I clinical trial to determine what dose of curcumin or piperine can be tolerated in people. The trial is not expected to begin accruing participants until spring.

Breast cancer statistics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society

Additional authors include Dean Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriel Dontu and Max Wicha, all from U-M

Funding was provided by the National Institutes of Health; curcumin and piperine were donated by Sabinsa Co.

Journal Reference:

1. Madhuri Kakarala, Dean E. Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriela Dontu and Max S. Wicha. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Research and Treatment, 2009; DOI: 10.1007/s10549-009-0612-x

Background Chinese medicine often targets more than one system and as such comprises several compounds, often in non-purified form, with treatments therefore consisting of whole extracts of herbs rather than isolated compounds. The additive and synergistic effects of the phytochemicals in OMN54, a novel mixture of extracts from three commonly used Chinese medicine components; Ganoderma lucidum, Salvia miltiorrhiza and Scutellaria barbata, were previously demonstrated to have potent anti-cancer activity. This study aims to test whether this heterogeneous, multifunctional and multitargeted agent has an acceptable toxicity profile. Methods We conducted preliminary and formal preclinical tolerability determination of OMN54 in Sprague-Dawley rats. In the preliminary study rats were given OMN54 by oral feeding daily for 14 days at doses of 1000mg/kg, 1750mg/kg, 2500mg/kg or 3000mg/kg per day. A subsequent daily dosing (x 28, 60, 120 or 180) formal toxicology study was conducted in male and female Sprague-Dawley rats at a dose of single dose of 2000mg/kg/day. Results Significant body weight loss was noted in one of the rats treated at 3000mg/kg/day, with decline beginning study day 11. This animal experienced mild GI toxicity in the form of diarrhoea. Gross observation indicated kidney damage (pale kidneys) in both this group and in one rat treated at 2500mg/kg/day. For the later studies, no body weight loss was noted over the course of the study. Blood counts and chemistry were not substantially altered following administration of OMN54, nor were there any findings on histological assessment of organs. Conclusion OMN54 was found to be well tolerated in rat models. OMN54 did not cause any microscopic, anatomic or pathologic changes in exposed animals at the concentrations and under the conditions employed in this study.

Chinese Medicine 2009, 4:22doi:10.1186/1749-8546-4-22

In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du-Tang (HLJDT), Gui-Zhi-Fu-Ling-Wan (GZFLW), and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1^- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria radix showed strong growth inhibition and induction of apoptosis in comparison with baicalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1^- immature myeloma cells rather than MPC-1⁺ myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB-, which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria radix have an antiproliferative effect on myeloma cells, especially MPC-1^- immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria radix by blocking IkB- degradation. (Blood. 2005;105:3312-3318)

Zi Ma, Ken-ichiro Otsuyama, Shangqin Liu, Saeid Abroun, Hideaki Ishikawa, Naohiro Tsuyama, Masanori Obata, Fu-Jun Li, Xu Zheng, Yasuko Maki, Koji Miyamoto, and Michio M. Kawano

From the Department of Bio-Signal Analysis, Applied Medical Engineering Science (AMES), Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan; and Department of Kampo Medicine, Molecular Science, and Applied Medicine, Yamaguchi University School of Medicine, Yamaguchi University, Yamaguchi, Japan.

Toxicology. 2009 Oct 7.

Burns JJ, Zhao L, Taylor EW, Spelman K.

Pinnacle Integrative Medicine, Phoenix, AZ, USA.

ScienceDaily (Nov. 5, 2009) — Green tea extract has shown promise as cancer prevention agent for oral cancer in patients with a pre-malignant condition known as oral leukoplakia, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, published online in Cancer Prevention Research, is the first to examine green tea as a chemopreventative agent in this high-risk patient population. The researchers found that more than half of the oral leukoplakia patients who took the extract had a clinical response.

Long investigated in laboratory, epidemiological and clinical settings for several cancer types, green tea is rich in polyphenols, which have been known to inhibit carcinogenesis in preclinical models. Still, clinical results have been mixed.

“While still very early, and not definitive proof that green tea is an effective preventive agent, these results certainly encourage more study for patients at highest risk for oral cancer,” said Vassiliki Papadimitrakopoulou, M.D., professor in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology, and the study’s senior author. “The extract’s lack of toxicity is attractive — in prevention trials, it’s very important to remember that these are otherwise healthy individuals and we need to ensure that agents studied produce no harm.”

In the Phase II dose-finding study, 41 M. D. Anderson oral leukoplakia patients were randomized between August 2002 and March 2008 to receive either green tea extract or placebo. Participants took the extract, an oral agent, for three months at one of three doses — 500 per meter squared of body mass (mg/m2); 750 mg/m2 or 1,000 mg/m2 — three times daily. To best assess biomarkers, participants also underwent a baseline and 12-week biopsy, an important component in the design of the study, the researchers say.

“Collecting oral tissue biopsies was essential in that it allowed us to learn that not only did the green tea extract appear to have benefit for some patients, but we pointed to anti-angiogenic effects as a potential mechanism of action,” said Anne Tsao, M.D., assistant professor in the Department of Thoracic/Head and Neck Medical Oncology, and the study’s first author. “While preliminary because our patient population was so small, this gives us direction for further study.”

Of those taking green tea at the two highest doses, 58.8 percent had a clinical response, compared with 36.4 percent in the lowest extract dose and 18.2 percent in the placebo arm. At an extended follow-up with a mean of 27.5 months, 15 participants had developed oral cancer, with a median time to disease development of 46.4 months.

Although not statistically significant, the green tea extract also improved histology and trended towards an improvement in a number of biomarkers that may play a vital role in predicting cancer development.

Another important finding, say the researchers, was that that the extract was well tolerated. Side effects, including insomnia and nervousness, were mostly seen in the high-dose group but produced no significant toxicity.

“While these are encouraging findings, much more research must be done before we can conclude that green tea may prevent oral or any other type of cancer. It’s also important to remind people that this trial enrolled very few participants who, at the highest dose levels took the equivalent of eight cups of green tea three times a day,” said Papadimitrakopoulo. “We need to further understand if green tea offers longer-term prevention effects for patients.”

Papadimitrakopoulo and Tsao think that future studies with green tea in this high-risk population should focus on participants being exposed to the supplement for a longer time period. The researchers also stressed that the green tea extract studied in this trial was never sold over-the-counter and/or the Internet, both of which are not highly regulated. Rather, the compound was exclusively developed as a pharmaceutical.

According to the American Cancer Society, more than 35,720 are expected to be diagnosed with oral and/or pharynx cancer and the five year survival rate is less than 50 percent.

The study was funded by Ito En, the company that produced the green tea extract.

In addition to Papadimitrakopoulou and Tsao, other M. D. Anderson authors on the study include: Waun Ki Hong, M.D., professor and chair of the Division of Cancer Medicine; Jack Martin, D.D.S., professor in the Department of Dental Oncology; Li Mao, M.D., adjunct professor and Xi Ming Tang, M.D., Ph.D. research scientist, both of the Department of Thoracic/Head and Neck Medical Oncology; Adel El-Naggar, M.D., Ph.D., professor in the Department of Pathology; Iganacio Wistuba, M.D., professor in the Department of Pathology-Research; Kirk Culotta, Phar M.D., Department of Pharmacy Pharmacology Research; Ann Gillenwater, M.D., professor in the Department of Head and Neck Surgery; J. Jack Lee, Ph.D., professor and Diane Liu, both of the Department of Biostatistics. Other authors include Yuko Sagesaka of Ito En, Ltd.