3^rd European Food Safety and Standards Conference

Biography

Biography: UGUR GOGUS

Abstract

Cancer, as one of the most common chronic metabolic diseases with its high death rate, seems not to have any particular diet or nutrition strategy, currently. Owing to its huge complexity in progress which involves many different reactions, pathways and proteins, in addition to a great number of bioactive compounds with their unique effects on these biochemical reactions, pathways and proteins, the necessity to clarify the interactions of the functional bioactive nutrient compounds in foods with the pathways and special proteins, has become more crucial than ever. Though we have an important number of chemotherapeutic drugs in the current status of cancer medicine, the drugs namely; sunitinib, sorafenib, 17-AAg, thapsigargin, eeyarestatin, bortezomib, metformin, tunicamycin, versipelostatin, brefeldin A, honokiol, paclitaxel, fulvestrant, doxorubicin, DBeQ, MKC-3946, MAL3-101, tamoxifen, nafoxidine, C1628, MG-132, reolysin (and many others…) with their well defined effect mechanisms and involvements in cancer pathways, their interactions with the bio-active nutrient compounds, like; I3C, lycopene, amygdalin, arginine, EGCG, vitamin D, kaempferol, genistein, tocopherol, lycopene, beta carotene, quercetin, apigenin and resveratrol, have not been properly reviewed. However, the design of an anti-cancer diet for a cancer patient during the treatment, can only be made according to the interactions between the anti-cancer drug and the bioactive compounds in the food. Each drug and each bioactive compound has different effects on the cancer triggering signalings; GRP78/BIP, beta catenin, Nrf2-keap1, ERK, Hedgehog, Rb/E2F, notch, PI3K/AKT/mTOR; the cancer triggering or inhibiting proteins; TNF, p38, p23, Bcl, GRP78, NF-kB, CDK, STAT3, Bax, MMP, Fas, erbB2, Foxo3, G6DP, STEAP, SOX2, galectine 3, CDC25, COX2, caspase, E2F3, AR, PRDX3, ERalpha, iNOS, PRDX3, IGF-1, HO-1, VEGF, GATA3, IL-1B, the enzyme systems; H₂O₂ fenton, phase II and CYP1A1. Therefore, first, the bioactive nutrient compounds which have the same effect with anti-cancer drug on these proteins, enzyme systems or signalings, should have been determined, and then, their food sources should form the anti-cancer diet for the given anti-cancer drug. The strategy to ‘what to eat and drink’ during cancer and cancer therapies, can only be made by knowing the bioactive nutrient compounds and their food sources and the anti-cancer drug, both of which effect the same pathways, proteins or signalings. For example, TNF recruits adaptor molecules that create a signaling to activate Mitogen-activated Protein Kinase Kinase Kinases (MAP3Ks) and transforming growth factor-B (TGFB) which is an essential regulator of cell survival. The activation of MAP3Ks, TGFB and TAK1 ( a serine/threonine kinase) by the cytokine leads to the activation of the inhibitor of kapa B alpha (IkBα) which inactivates NF-kB, the protein complex that controls DNA transcription, cytokine production and cell survival due to the antiapoptotic factor FADD45B. Briefly, TNF may act as tumor enhancer via the activation of MAP3Ks, TGFB, TAK1 and NF-kB. One of the anti-cancer effects of kaempferol (a flavonoid) is to inhibit TNF, like the anti-cancer drugs; infliximab, adalimumab, narasin, honokiol, vorinostat, tribromsalan, bithionol, celecoxib.. During  such  treatments, curcumin (e. g. Curcuma longa and cinnamon) and  resveratrol rich foods, e. g. orange, grape, blueberrires, strawberries, lemon, tea and penut, should be included into the anti-cancer diet, since curcumin and resveratrol, like kaempferol and kaempferol rich foods (e.g. tea, broccoli, apple, blueberries, kale, beans, endive, leek, tomato, grape, parsley, plum, apricot, capsicum pepper, onion, cherry, celery, plum, strawberries, propolis, herbs; Gingko biloba, Tilia spp., Equisetum spp., Moringa oleifera and Sophora japonica), may form a synergy with the TNF-blocking anti-cancer drugs, since all of them inhibit TNF, and hence leading to a much stronger apoptosis. But arginine/NO(nitric oxide) treatments/arginine / NO supplementation or arginine rich foods, should be adviced to be avoided, the foods like; egg white, turkey breast, beef, ground red meat, lupin, soybean, nuts, seeds, mollusk, chickpea, lentil, chicken meat, pork meat, sesame and beef meat, since arginine and NO activates both TNF and NF-kB and therefore, may decrease the anti-cancer potential of the treatments which administer the mentioned TNF/Nf-kB inhibitors. On the other hand, the same cytokine may have opposite effect, inducing apoptosis, based on its relation with the apoptotic enzymes, Caspases. TNF receptor-associated death domain protein (TRADD) and a serine/threonine kinase called receptor interacting protein kinase (RIPK)-1, form a signaling complex that recruits an adaptor protein known as Fas-associated death domain protein (FADD), forming a disc which activates Caspases 8, 10 and 6, causing apoptosis. Accordingly, kaempferol and kaempferol rich foods, curcumin and resveratrol and their rich sources, may be advised during the treatment using anti-cancer drugs which activate Caspases, the anti-cancer drugs namely;  costunolide (the stem bark of Magmolia sieboldii), cisplatin, mitomycin c, garcinol, brefeldin A, valinomycin, piceatannol, kinetin riboside, lipase inhibitor, THL, imiquimod, SC 560, romidepsin, ouabain, digoxin, proscillaridin A, borrelidin, sanguinarine, bortezomib, MT-21, lonidamine, K858, saikosaponin A, CIL-102, and prodigiosin, forming a synergy to show much stronger anti-cancer potential via the activation of Caspases.  Briefly, the determination of the foods in an anti-cancer diet can only be made by analyzing the bio-active nutrient compound and anti-cancer drug interactions. In the presentation of the review which used more than 2000 studies, 186 of which are case and follow-up studies, the interactions of each of the bioactive nutrient compounds and their food sources, with each anti-cancer drug, have been analyzed and documented. As a result, a unique anti-cancer diet for each group of anti-cancer drugs, in which both the diet and the drug/drugs target the same pathway/pathways, protein/proteins and/or enzyme systems, was designed. Otherwords, a map of ‘food and anti-cancer drug’ which indicates to the ‘food for drug’ was designed. In the presentation, these interactions of the 15 bio-active nutrient compounds; I3C, lycopene, amygdalin, arginine, EGCG, vitamin D, kaempferol, genistein, tocopherol, lycopene, beta carotene, quercetin, apigenin, sulforaphane and resveratrol, with the currently most common anti-cancer drugs, will have been discussed.

Some of the most important reasons for the conflicting results of anti-cancer researches about the bioactive nutrient compounds, like ‘the dose’, just like in the example of ‘high dose arginine and NO (>400 µM) with a strong anti-cancer effect’, while the lower doses are ineffective, will also be documented in the presentation.

Finally, one of the biggest myths in cancer nutrition; ‘fructose feeds and triggers cancer cells as the only culprit and thus,, it should be out of list’, which is often enforced by all the current media, will have been disproven since, almost all of the foods contain fructose or glucose (which finally is converted into fructose!) and hence, fructose limitation cannot be practical, reasonable and scientific!. Moreover, glutamin, a non essential amino acid, which exists in almost all animal origin foods, is much more utilized than glucose by cancer cells. Assuming that the fructose and glutamin are the only culprits, the elimination of glutamin and fructose rich foods from the diet will not be rational since there will be nothing left much!. More important is that, such enforcements and misdirections made by some part of media and scientists, neglect the antioxidant vitamins, minerals, flavonoids, essential fatty acids and bio-active nutrient compounds, in these fructose and/or glutamin rich foods, all of which have got important anti-cancer effects. These myths and misdirections will also be pointed out in the presentation.

In the last part, the fundemental details of an anti-cancer diet for a particular anti-cancer drug, the skeleton of a healthy diet to prevent from the risk of cancer, the external and internal factors which determine the anti-cancer potential of the bioactive compound, will have been summarized.