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.

An article, published in Comprehensive Reviews in Food Science and Food Safety, evaluated current research on flaxseed and any potential benefits it may have against diabetes and certain cancers.

Flaxseed has been the focus of increased interest in the field of diet and disease research due to the potential health benefits associated with some of its biologically active components: oil containing approximately 59 per cent a-linolenic acid (ALA) and the presence of plant lignan secoisolariciresinol diglycoside (SDG).

The authors, researchers from Canada, England and China, summarized that the health benefits from flaxseed ligans are due to their antioxidant activity, primarily from the hydroxyl radical scavengers and also due to their estrogenic and antiestrogenic compounds and the structural similarity to 17-b-estradiol.

Their paper states that SDG, once ingested, is converted in the colon into active mammalian lignans, enterodiol (END) and enterolactone (ENL) which have shown promise in reducing growth of cancerous tumors, especially hormone-sensitive ones such as those of the breast, endometrium, and prostate.

They concluded that flaxseed lignans could be a significant part of a treatment regimen for cancer based on the large number of small scale studies but they stress that further research is needed in clinical settings to support the role of flaxseed in cancer prevention in human populations.

And they called for further research to be undertaken to assess any potential adverse effects from over consumption of the seed: “More in vivo studies are needed to ascertain the propitious effects of lignans secoisolariciresinol and to see if there are any dangers in possible overdoses.”

Breast cancer

Studies (Adlercreutz and others 1992; Saarinen and others 2000) on flaxseed benefits for breast cancer that the authors reviewed showed the presence of flaxseed lignans in MCF-7 tumors and observed lignan binding to estrogen receptors (ER). This suggests, said the reviewers, that the lignan function may be ER-mediated.

“Although the lignans have been shown to be protective against breast cancer, minor structural alterations may influence overall activity (Saarinen and others 2005). Thus, many of the aforementioned benefits might be the results of specific structural features needed for lignans to bind to ER,” they claim.

Prostate cancer

Evaluating studies looking at flaxseed ligans effect on prostate cancer, the researchers said that lignans enterodiol and enterolactone were believed to be partly responsible for the growth inhibition of 3 human prostate cancer cell lines.

They report that Morton and others (1997) found that higher enterolactone levels in prostatic fluid were associated with populations with a low risk of prostate cancer.

Another small clinical study, note the reviewers, showed that prostate cancer cell proliferation decreased and apoptosis increased in men fed 30 g of flaxseed per day, and they reported that a subsequent study by the same researchers supported the role of flaxseed in combination with a low-fat diet as a means to control prostate growth.

Although not as extensively reviewed, the reviewers also report that flaxseed has been shown to inhibit colon and skin cancers in cell cultures and animal studies that have been conducted in this area.

Diabetes

Low-glycemic-index foods containing soluble fibre may not only prevent certain metabolic ramifications of insulin resistance, but also reduce insulin resistance, noted the authors, citing a study whereby flaxseed was shown to reduce the postprandial blood glucose response in humans.

“A consumption of 50 g/d ground flaxseed by young females over a 4-wk period caused a reduction in blood glucose levels (Cunnane and others 1993). Similar findings were observed in postmenopausal women fed a 40 g/d flaxseed fortification diet (Lemay and others 2002),” they stated.

Safety

There has been concern noted over certain components of flaxseed such cyanogenic glycosides, said the reviewers.

The authors stress that cyanogenic glycosides are not exclusive to flaxseed and are found in brassica vegetables and cassava, with many of the health concerns regarding cyanogenic glycosides stemming from studies showing that cassava was toxic to animals and humans.

“Cassava contains significantly more cyanogenic glycosides than flaxseed. Furthermore, the release of hydrogen cyanide from flaxseed would be minimal and below the toxic or lethal dose.

At the recommend daily intake of about 1 to 2 tablespoons, approximately 5 to 10 mg of hydrogen cyanide is released from flaxseed, which is well below the estimated acute toxic dose for an adult of 50 to 60 mg inorganic cyanide and below the 30 to 100 mg/d humans can routinely detoxify,” stress the authors.

They also cite a study from Daun and others (2003) that reported that a person would have to consume 8 cups (1 kg) of ground flaxseed to achieve acute cyanide toxicity.

Source: Comprehensive Reviews in Food Science and Food Safety
Published online ahead of print
Title: Flaxseed Lignans: Source, Biosynthesis, Metabolism, Antioxidant Activity, Bio-Active Components, and Health Benefits
Authors: A. Tour´e, X. Xueming