Dr. Ron’s Research Review – February 9, 2010

© 2010

 

This week’s research review begins with a few articles on breast cancer (flaxseed to lower 2/16, curcumin and melatonin) and an article on male breast cancer. A recent study shows that chrysin may be useful for IBD. Next are few articles on porphyria.

The most important article was published in JAMA - Soy food intake and breast cancer survival

Flaxseed

Flaxseed is a rich source of dietary lignans.  Forty-three postmenopausal women consumed 7.5 g/day of ground flaxseed for 6 wk, followed by 15 g/day for an additional 6 wk. The mean urinary level of 16alpha -hydroxyestrone (16alpha -OHE1) was higher at the end of 12 wk compared to baseline (change of 1.32 ug/day, P = 0.02). There was no significant change in 2-OHE1 excretion. Mean urinary excretion of 2-methoxyestradiol was also lower at 12 wk than at baseline (P = 0.03). (Sturgeon, Volpe et al. 2010)

 

The most interesting article is: “Breast cancer patients unknowingly dosing themselves with estrogen by using topical moisturizers”

 

Dr. Ron

 

Soy food intake and breast cancer survival

            (Shu, Zheng et al. 2009) Download

CONTEXT: Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients. OBJECTIVE: To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence. DESIGN, SETTING, AND PARTICIPANTS: The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information. MAIN OUTCOME MEASURES: Total mortality and breast cancer recurrence or breast cancer-related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable. RESULTS: During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor-positive or -negative breast cancer and was present in both users and nonusers of tamoxifen. CONCLUSION: Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

 

Effect of flaxseed consumption on urinary levels of estrogen metabolites in postmenopausal women

            (Sturgeon, Volpe et al. 2010) Download

Flaxseed is a rich source of dietary lignans. It has been hypothesized that lignans may decrease breast cancer risk through modulation of endogenous hormone levels. The aim of this study was to determine the effect of flaxseed supplementation on urinary levels of estrogen metabolites that may be involved in the development of breast cancer. Forty-three postmenopausal women participated in this 12-wk preintervention-postintervention study. Participants consumed 7.5 g/day of ground flaxseed for 6 wk, followed by 15 g/day for an additional 6 wk. The mean urinary level of 16alpha -hydroxyestrone (16alpha -OHE1) was higher at the end of 12 wk compared to baseline (change of 1.32 ug/day, P = 0.02). There was no significant change in 2-OHE1 excretion. The mean urinary level of the 2-OHE1/16alpha -OHE1 ratio was lower at the end of 12 wk compared to baseline (change of -1.1, P = 0.02). Mean urinary excretion of 2-methoxyestradiol was also lower at 12 wk than at baseline (P = 0.03). Based on the current paradigm of the effects of estrogen metabolism on breast cancer risk, the regimen of dietary flaxseed intake used in this study did not appear to favorably alter breast cancer risk through shifts in estrogen metabolism pathways in postmenopausal women.

 

Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer

            (Labbozzetta, Notarbartolo et al. 2009) Download

We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.

 

Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

            (Grant, Melan et al. 2009) Download

Recent studies have suggested that the pineal hormone melatonin may protect against breast cancer, and the mechanisms underlying its actions are becoming clearer. Melatonin works through receptors and distinct second messenger pathways to reduce cellular proliferation and to induce cellular differentiation. In addition, independently of receptors melatonin can modulate oestrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity. The fact that melatonin works through a myriad of signalling cascades that are protective to cells makes this hormone a good candidate for use in the clinic for the prevention and/or treatment of cancer. This review summarises cellular mechanisms governing the action of melatonin and then considers the potential use of melatonin in breast cancer prevention and treatment, with an emphasis on improving clinical outcomes.

 

Biomarkers, critical disease pathways, drug targets, and alternative medicine in male breast cancer

            (Barh 2009) Download

While breast cancer (BC) is commonest malignancy among female with highest death rate, male breast cancer (MBC) is very rare but exhibits highest cancer specific death in men and the incidences of MBCs are rising rapidly. Due to rarity of the disease, no detail information about biomarkers and drug targets available and because of late diagnosis and rarely understood the pathogenesis at molecular level, the treatment of MBC is also not yet standardized. Though the MBC biology, pathogenesis, and the clinical outcomes resembles with female breast cancer (FBC), they are quite unique in many aspects. Therefore, the uses of FBC specific drugs for treatment of MBC are not only dissatisfactory but also increases mortality rate due to severe side effects of these conventional drugs. To avoid side effects of usual therapeutic drugs, new drugs and their targets should be identified and evaluated, where the dietary phytochemicals may be the alternative of currently used drugs. Similarly, an integrated strategy and pharmacogenomics approach is now essential to fight against this malady. This article will deal with different aspects of MBC including biomarkers, pathways, drug targets, and common dietary phytochemicals as effective alternatives of conventional chemotherapeutic drugs for targeted therapy without any side effect.

 

Chrysin, a natural flavone, improves murine inflammatory bowel diseases

            (Shin, Kwon et al. 2009) Download

Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in many plants. It has previously been shown to be an anti-tumor agent. In this study, we investigated whether chrysin could alleviate the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice and whether chrysin has an inhibitory effect on nuclear factor (NF)-kappaB activation in vitro. A significant blunting of weight loss and clinical signs was observed in DSS-exposed, chrysin-treated mice when compared to vehicle-treated mice. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines. In addition, chrysin inhibited tumor necrosis factor (TNF)-alpha-induced activation of NF-kappaB in IEC-6 cells. These findings suggest that chrysin exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of NF-kappaB activation.

 

Serum 25-hydroxyvitamin D in erythropoietic protoporphyria

            (Holme, Anstey et al. 2008) Download

BACKGROUND: Vitamin D, produced by the action of sunlight on skin, is an important hormone for calcium homeostasis and has been implicated as tumour-protective agent. Some previous studies of photosensitive patients who actively avoid sunlight have failed to show convincing evidence of vitamin D insufficiency. OBJECTIVES: The aim of this study was to characterize the vitamin D status of a large cohort of patients with erythropoietic protoporphyria (EPP). METHODS: U.K. patients with EPP were recruited prospectively and seen locally by a single study investigator. A blood sample was taken for vitamin D assay. All blood analyses were performed in the same laboratory. RESULTS: A cohort of 201 patients with known EPP was seen over a 7-month period between January and July. Thirty-four patients (17%) were deficient in vitamin D and 126 (63%) had insufficient vitamin D. Both insufficiency and deficiency were significantly associated with the total erythrocyte protoporphyrin concentration and inversely with the time in minutes to the onset of symptoms following sunlight exposure. CONCLUSIONS: This is the first report of significant levels of vitamin D deficiency and insufficiency in a large cohort of patients with a photodermatosis. Such individuals are at risk of associated adverse events. In future, clinicians should consider monitoring 25-hydroxyvitamin D levels and instigating oral supplementation or dietary advice if appropriate.

 

Variegate porphyria induces plasma and neutrophil oxidative stress: effects of dietary supplementation with vitamins E and C

            (Ferrer, Tauler et al. 2010) Download

Our aim was to analyse the influence of variegate porphyria (VP) on the antioxidant defenses and markers of oxidative damage and inflammation in plasma and neutrophils and the effects of dietary supplementation with vitamins E and C on these parameters in plasma, neutrophils and erythrocytes. Twelve women affected by VP and twelve pair-matched healthy control women participated in a double-blind crossover study. Each participant took 50 mg/d of vitamin E and 150 mg/d of vitamin C, or a placebo, for 6 months, by consuming an almond-based beverage as the vehicle. Women affected by VP presented higher C-reactive protein and malondialdehyde (MDA) circulating levels. Plasma antioxidant defenses were not different between porphyric and control women. Neutrophils from VP women presented decreased catalase (CAT) and glutathione reductase (GR) activities together with increased protein carbonyl levels. Reactive oxygen species (ROS) production from stimulated neutrophils was also higher in porphyric women than their controls. Dietary supplementation was effective in increasing alpha-tocopherol levels in neutrophils and in reducing MDA levels in plasma. Erythrocyte CAT and GR activities were enhanced by the enriched beverage only in the control subjects. In conclusion, women affected by VP present a situation of inflammation, plasma oxidative damage and neutrophils more primed to the oxidative burst, with decreased antioxidant activities and increased ROS production capabilities and protein oxidative damage. Dietary supplementation with vitamin E (50 mg/d) and vitamin C (150 mg/d) for 6 months decreased plasma oxidative damage and enhanced the erythrocyte activities of CAT and GR.

 

Breast cancer patients unknowingly dosing themselves with estrogen by using topical moisturizers

            (Olson, Link et al. 2009) Download

 


References

Barh, D. (2009). "Biomarkers, critical disease pathways, drug targets, and alternative medicine in male breast cancer." Curr Drug Targets 10(1): 1-8.

Ferrer, M. D., P. Tauler, et al. (2010). "Variegate porphyria induces plasma and neutrophil oxidative stress: effects of dietary supplementation with vitamins E and C." Br J Nutr 103(1): 69-76.

Grant, S. G., M. A. Melan, et al. (2009). "Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives." Expert Rev Mol Med 11: e5.

Holme, S. A., A. V. Anstey, et al. (2008). "Serum 25-hydroxyvitamin D in erythropoietic protoporphyria." Br J Dermatol 159(1): 211-3.

Labbozzetta, M., M. Notarbartolo, et al. (2009). "Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer." Ann N Y Acad Sci 1155: 278-83.

Olson, A. C., J. S. Link, et al. (2009). "Breast cancer patients unknowingly dosing themselves with estrogen by using topical moisturizers." J Clin Oncol 27(26): e103-4.

Shin, E. K., H. S. Kwon, et al. (2009). "Chrysin, a natural flavone, improves murine inflammatory bowel diseases." Biochem Biophys Res Commun 381(4): 502-7.

Shu, X. O., Y. Zheng, et al. (2009). "Soy food intake and breast cancer survival." JAMA 302(22): 2437-43.

Sturgeon, S. R., S. L. Volpe, et al. (2010). "Effect of flaxseed consumption on urinary levels of estrogen metabolites in postmenopausal women." Nutr Cancer 62(2): 175-80.