Jacob Schor ND FABNO
December 5, 2009
Somewhere around written on a scrape of paper and tucked between the pages of a cookbook is my fruitcake recipe. I’ve been searching around for it and just recalled that it’s posted on our website as part of a newsletter a few years back. Here it is:
Of course rereading this old newsletter on the synergistic action of phytochemicals begs one to see if anything new has been published in this realm, an easy enough thing to do. A simple search of the NIH’s National Library of Medicine can be done by going to www.PubMed.gov.
Looking for articles on, “Synergy AND Phytochemicals” yields more than a dozen journal references, some of which appear interesting.
Aftab and Vieira from Simon Fraser University in an article that came out just a few weeks back, November 2009, look at the interaction of curcumin with other plant chemicals. Combining curcumin with resveratrol extracted from grape skins resulted in a synergistic antioxidant effect, significantly greater than predicted by measuring and adding individual effects of each extract:
“Curcumin and resveratrol together (5 muM each) resulted in a synergistic antioxidant effect: 15.5 +/- 1.7% greater than an average of individual activities. This synergy was significantly greater (p < 0.05; about 4-fold) than that of curcumin together with the flavonol quercetin.”
A few weeks prior in October 2009, two researchers from New York Medical College, Hsieh and Wu , published and equally interesting paper on the synergistic action of green tea with genestein, a soy bean constituent, and quercetin at inhibiting prostate cancer. Interestingly they found that the combination did have a significant synergistic effect but only if a small amount of blood serum was also added to the culture. This would suggest some factor contained in the blood is necessary for these constituents to act synergistically: “…. serum added to culture medium might affect uptake, bioavailability and biological efficacy of dietary phytochemicals.”
This is interesting in the light of a paper by the same authors published exactly a year earlier. In the earlier paper they looked for synergistic effect of green tea, resveratrol and gamma-tocotrienol at inhibiting growth of ER+ breast cancer cells and found little evidence of any. One has to wonder if they would have seen effect in this earlier experiment if they had known to add the blood serum to the cell cultures?
A 2007 paper from Australia revives my recent interest in avocadoes. These fine researchers tell us a toxin extracted from avocado leaves called persin has a synergistic effect with the drug tamoxifen at treating breast cancer. Their results are exciting for several reasons. First, the synergistic effect but second the combination appears to have desired effects on breast cancer cells regardless of the ER status. The combination affected ER- cells whereas tamoxifen is typically thought only useful on ER+ breast cancer cells.
We could go on with this all day but if I’m going to get these in the oven I need to get to the store to buy some dried cherries to soak. The trick discovered via Cooks Illustrated a few years back in making fruitcake is to presoak dried fruit in rum. Doing this bypasses the need to age the baked fruitcakes slowly basting them in rum for weeks and weeks until ready to eat. With the rum soaked dried fruit method it takes only a few days for the rum to leach out into the cake and yield a decent finished cake.
Other past newsletters and articles that include recipes now have their own section in our archive listings:
Phytother Res. 2009 Nov 19. [Epub ahead of print]
Antioxidant activities of curcumin and combinations of this curcuminoid with other phytochemicals.
Aftab N, Vieira A.
Laboratory for Nutrition & Metabolic Research, K9600 Simon Fraser University, Burnaby, BC, Canada.
Biomedical investigations of curcumin (and curcuminoids) have provided evidence of a wide range of molecular and cellular activities, most related to redox reactions and signal transduction. The main goal of the present study was to compare antioxidant activities of curcumin with those of resveratrol, a polyphenol present in some dietary plants such as Vitis vinifera (L.) and Arachis hypogaea (L.) and many other, non-dietary plants. Combinations of the two were also examined for potential synergism in a heme-enhanced oxidation reaction. Curcumin exhibited antioxidant effects at all time points (1-5 min; 10 muM), e.g., 30.5 +/- 11.9% (SEM) oxidation relative to controls without phytochemicals (p < 0.01) at 3 min, a time chosen for comparisons. The same concentration of resveratrol exhibited about half of curcumin's activity. Curcumin and resveratrol together (5 muM each) resulted in a synergistic antioxidant effect: 15.5 +/- 1.7% greater than an average of individual activities. This synergy was significantly greater (p < 0.05; about 4-fold) than that of curcumin together with the flavonol quercetin. In conclusion, curcumin is a potent antioxidant in a reaction that may be relevant to in vivo toxicity. In relation to two other well-known antioxidants, curcumin shows significantly greater synergism with resveratrol than with quercetin. Copyright (c) 2009 John Wiley & Sons, Ltd.
Anticancer Res. 2009 Oct;29(10):4025-32.
Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin.
Hsieh TC, Wu JM.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Prostate cancer (CaP) is a significant cause of death in American men. While men residing in Asia show a lower incidence of hormone-refractory prostate cancer (HRPC) compared to Caucasian males, Asian men who move to and live in the United States and adopt a western lifestyle have HRPC rates indistinguishable from Caucasian males. These findings suggest that Asian diets contain ingredients that might protect against the development of HRPC. The identity and mechanisms of such HRPC protective agents remain to be elucidated. An Asian diet may confer protection against HRPC owing to functional synergy between bioactive dietary agents, thus broadening the chemopreventive index, with increased distinct anticancer properties and decreased untoward effects. Here, whether or not a combination of epigallocatechin gallate (EGCG), genistein and quercetin, phytochemicals present in a traditional Asian diet, might exert synergy in controlling proliferation and gene expression was investigated in CWR22Rv1 CaP cells, an in vitro model mimicking CaP transition from AD (androgen dependence) to HRPC. Cell proliferation was inhibited approximately 40%, approximately 15% and approximately 20%, respectively by 2.5 microM EGCG, genistein and quercetin used alone. The co-administration of 2.5 microM of these phytochemicals suppressed proliferation synergistically in the CWR22Rv1 cells maintained in RPMI-1640 supplemented with 10% fetal bovine serum, but not in the cells maintained as serum-free cultures. Synergy in the expression of androgen receptor, tumor suppressor p53 and detoxification enzyme quinone reductase type 1, denoted NQO1, was also observed for the combined phytochemicals. These results demonstrate the feasibility of developing a diet-based combinatorial approach for CaP prevention and treatment and raise the possibility that serum added to culture medium might affect uptake, bioavailability and biological efficacy of dietary phytochemicals.
Int J Oncol. 2008 Oct;33(4):851-9.
Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells.
Hsieh TC, Wu JM.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Numerous dietary phytochemicals have shown anti-breast carcinogenic activities when tested in vitro; however, in most cases, the demonstrated efficacy of individual phytochemicals requires doses not readily achievable in vivo. Therefore, whether diets might exert translational promises and benefits in clinical settings and prevention of breast cancer remain unclear. Since cancer cells are endowed with complex, redundant, converging and diverging pathways spanning both the genetic and metabolic networks that are not merely replicates of those in normal cells, it is of interest to test whether a multicomponent approach involving lower, physiologically relevant doses of natural dietary agents may be developed as a chemopreventive strategy for breast cancer. Herein, we investigated, using the estrogen receptor-positive MCF-7 breast cancer cells as a model, whether the combination of epigallocatechin gallate (EGCG), resveratrol and gamma-tocotrienol at suboptimal doses elicits synergism in suppressing cell proliferation, modulating gene expression, and increasing antioxidant activity, as compared to each of the three phytochemicals added alone. The results showed that there was a approximately 33, 50 and 58% inhibition of cell proliferation by > or =50 microM EGCG, > or =25 microM resveratrol and > or =10 microM gamma-tocotrienol, respectively, added as a single agent. When a suboptimal dose (10 microM) of each phytochemical was used, a significant additive effect in suppression of cell proliferation was observed with the combination of resveratrol and gamma-tocotrienol whereas the three phytochemicals added together did not produce more pronounced inhibition of cell proliferation. A significant additive effect in reducing cyclin D1 and bcl-2 expression was found when gamma-tocotrienol was added with either EGCG or resveratrol. Functional synergism among the three phytochemicals was only observed in the induction of quinone reductase NQO1. These results suggest that diet-based protection against breast cancer may partly derive from synergy amongst dietary phytochemicals directed against specific molecular targets in responsive breast cancer cells, and provide support for the feasibility of the development of a diet-based combinatorial approach in the prevention and treatment of breast cancer.
Mol Cancer Ther. 2007 Oct;6(10):2777-85. Epub 2007 Oct 3.
Synergistic cytotoxicity between tamoxifen and the plant toxin persin in human breast cancer cells is dependent on Bim expression and mediated by modulation of ceramide metabolism.
Roberts CG, Gurisik E, Biden TJ, Sutherland RL, Butt AJ.
Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.
Phytochemicals have provided an abundant source of novel therapeutics for the treatment of human cancers. We have previously described a novel plant toxin, persin, derived from avocado leaves, which has unique in vivo actions in the mammary epithelium and Bim-dependent, cytotoxic effects in human breast cancer cells in vitro. Compounds structurally similar to persin, such as the polyunsaturated fatty acid, conjugated linoleic acid, can attenuate steroid hormone receptor signaling and modulate the response of breast cancer cells to antiestrogens. Here, we provide evidence that persin may have similar effects by showing its potent proapoptotic synergy with the antiestrogen 4-hydroxytamoxifen. However, although persin transcriptionally down-regulates estrogen receptor (ER) expression, unlike conjugated linoleic acid, it also shows efficacy in ER-negative breast cancer cells, both alone and in combination with 4-hydroxytamoxifen, whereas normal breast epithelial cells are unaffected, suggesting it may act via a distinct, ER-independent mechanism. These proapoptotic synergistic interactions are associated with increased de novo ceramide synthesis and are dependent on expression of the proapoptotic protein Bim. These data show that persin should be further investigated as a potential novel cancer therapeutic agent because it significantly enhances the sensitivity of breast cancer cells to the cytotoxic effects of tamoxifen, regardless of their ER status, while displaying apparent specificity for the malignant phenotype.