Rhubarb and breast cancer risk

Studies have not established the effect of rhubarb on breast cancer

Rhubarb is a good source of vitamin C, calcium, magnesium and dietary fiber. Rhubarb contains the carotenoids lutein and zeaxanthin, which have been shown to have some anticancer activities. Rhubarb has also been shown to have anti-inflammatory, anti-atherosclerosis and plaque-stabilizing actions in laboratory animals.

Cancer-related effects of eating rhubarb

Rhubarb contains the polyphenol (Z)-3,5,4-Trimethoxystilbene, a resveratrol analog that has been shown to arrest the growth of human colon cancer cells in a dose dependent manner. Piceatannol, another polyphenol in rhubarb, has been shown to exert immunosuppressive, antileukemic, and antitumorigenic activities, including inhibition of the proliferation of human bladder and prostate cancer cells. The most abundant anthraquinone of rhubarb, emodin (which has traditionally been used as a laxative) has been shown to induce apoptosis in human pancreatic, liver, prostate and breast cancer cell lines. Rhein, another component of rhubarb, has been found to induce apoptosis of nasopharyngeal cancer cells. Because rhubarb typically does not comprise a large portion of the diet of any group of people, there are no population-based studies that specifically isolate any associations between consuming rhubarb and the risk of cancer.

Additional comments

Rhubarb is a component of Essiac™ tea, a herbal tea sometimes used as a cancer treatment. While the tea has been shown in the laboratory to have potent antioxidant and DNA-protective activity, one careful study found no observable action of Essiac™ against prostate cancer cells.

Rhein, a constituent of rhubarb, is the major component of several traditional Chinese herbal medicines, including laxatives and stomach remedies. Rhein herb-drug interactions, especially cytochrome P450 (CYP)-mediated interactions, may cause an enhancement or attenuation in the efficacy of prescription drugs.

There are some available rhubarb-based herbal remedies designed to treat menopausal symptoms in women and containing the phenolic gallylglucoside lindleyin. Lindleyin is a phytoestrogen which has demonstrated estrogenic activity. We recommend against using such remedies for breast cancer patients, survivors and those at high risk for breast cancer since their safety has not been demonstrated. In particular, it is possible that lindleyin could promote beast cancer through its estrogenic activity. Rhubarb should not be consumed by pregnant women since it may trigger uterine contractions.

Consuming large amounts of rhubarb to obtain the possible benefit of its anticancer components would be impractical since a great deal of sweetener is required to counteract rhubarb's sourness and since the gastrointestinal effects could be overwhelming. However, we would not recommend consuming concentrated rhubarb extracts or pills since their safety and efficacy have not been established.

Rhubarb leaves should not be consumed since they are poisonous. People with a history of kidney stones should avoid rhubarb, since consumption of rhubarb has been shown to increase urinary oxalate due to the plant's relatively high oxalate content.

Tags: Chinese, cytochromeP450, essiacTea, phytoestrogens, pregnancy, resveratrol, rhubarb

Selected studies

Effects of emodin on the gene expression profiling of human breast carcinoma cells Cancer Detection and Prevention, January 2009

The current study was designed to elucidate emodin's action in BCap-37 breast cancer cells. A microarray comprised of 458 known genes, including death receptors, death kinases, calpains, granzymes, caspases, DNA fragmentation proteins and Bcl-2 family, was used. In addition, the relevant emodin target genes were further evaluated via real-time quantitative PCR and Western blot analysis. Gene expression profiling in human breast cancer BCap-37 cells was found to be altered when exposed to emodin. Thirty genes that were either induced or repressed in response to emodin-induced apoptosis also were identified. Emodin was found to have no effect on caspases. The authors also conclude that the p53 pathway may cooperate with the IGF-2 pathway, resulting in emodin-induced apoptosis by means of disruption of the mitochondrial signaling pathway.

Anti-mitotic properties of resveratrol analog (Z)-3,5,4-trimethoxystilbene Biofactors, December 2008

The molecule (Z)-3,5,4-Trimethoxystilbene was prepared in a 3-step process with good overall yield. (Z)-3,5,4-Trimethoxystilbene is a polyphenol found in the following five plants: Virola cuspidata; Centipeda minima; Schoenus nigricans; Virola elongata; and Rheum undulatum. The isomerisation from the (E)- to the (Z)-isomer was performed using UV irradiation. The biological activity of the molecule was tested in the Caco-2 human colon cancer cell line. Growth was found to be completely arrested at a 0.4 M level of (Z)-3,5,4-trimethoxystilbene. The authors conclude that this molecule is 100 times more active than resveratrol or (E)-3,5,4-trihydroxystilbene and that the mechanism of this process involves inhibition of tubulin polymerization in a dose dependent manner.

Evaluation of the Antiproliferative Effects of Essiac™ on In Vitro and In Vivo Models of Prostate Cancer Compared to Paclitaxel Nutrition and Cancer, July 2007

The current study evaluated the Essiac™, a herbal tea, for its antiproliferative effects on prostate cancer. Crystal violet assay and analysis of cell cycle distribution by flow cytometry were used to test the cytotoxic effects of Essiac in vitro. No differences between the control and treatment groups were observed. The chemotherapy drug Paclitaxel was used as a positive control in cell cycle analysis. Paclitaxel was the only treatment that showed significant effects on cell cycle distribution. Toxicity in nude mice was tested, as well as effectiveness in inhibiting PC-3 xenograft growth. No toxicity or tumor size difference was found using doses up to 240 mg/kg over 28 days, except for the Paclitaxel-treated positive control group. Ki-67 and PCNA expression was analyzed in the treated tumors, but no difference in expression of either marker was observed. The authors conclude that Essiac has no marked antiproliferative effect in the prostate cancer models tested.

Trial of Essiac to ascertain its effect in women with breast cancer Journal of Alternative and Complementay Medicine, December 2006

The primary objective of the current study was to determine the difference in health-related quality of life, as assessed by the Functional Assessment of Cancer Therapy Breast Cancer Version, between new Essiac users (since breast cancer diagnosis) and those who have never used Essiac. The study also evaluated differences in depression, anxiety, fatigue, rate of adverse events, and prevalence of complications or benefits associated with Essiac during breast cancer treatment. The study, which was retrospective, included 510 women randomly chosen from the Ontario Cancer Tumour Registry with a diagnosis of primary breast cancer during 2003. The women were taking relatively low doses of Essiac (total daily dose 43.6 +/- 30.8 mL), corresponding to the directions found on most Essiac products. Essiac was found to be associated with negative effects on physical well-being and relationship with doctor. With the exception of changes in these subscales, Essiac did not have a significant effect on health-related quality of life or on mood states. These results might be attributed in part to the fact that the group of users were on average younger women with more advanced stages of breast cancer. This subgroup of patients has been demonstrated to be at a significantly increased risk for negative mood states and a decreased sense of well-being. The authors conclude that Essiac does not appear to improve health-related quality of life or mood states in breast cancer patients.

The phytochemical lindleyin, isolated from Rhei rhizoma, mediates hormonal effects through estrogen receptors Journal of Endocrinology, November 2002

The current study examined the effects of various herbal extracts on estrogen receptor-alpha and estrogen receptor-beta isoforms. The herbal extract Rhei rhizoma (rhubarb) was found to act as an agonist to both estrogen receptor-alpha and estrogen receptor-beta isoforms, possibly through the action of the phytochemical lindleyin, a major component of rhubarb. The estrogen receptor antagonist 4-Hydroxytamoxifen was found to completely reverse the estrogenic activity of lindleyin. In addition, lindleyin was found to bind to estrogen receptor-alpha in vitro. The in vivo effect of rhubarb extract was evaluated using a vitellogenin assay system in the Japanese medaka, a freshwater fish. Marked increases in serum vitellogenin levels were found in male medaka exposed to rhubarb extract. The authors conclude that lindleyin, a component of some herbal medicines, is a phytoestrogen and could trigger many of the biological responses evoked by the physiological estrogens.