Dietary Agents for cancer therapy and their molecular targets
Jacob Schor, ND
September 19, 2007
On the hunt at Costco this past week, I tracked down a BlendTec home blender, probably the wildest and most expensive blender I will ever own. With a three-watt motor, it can puree a quart of ice cubes, fruit and miscellaneous ingredients into a smoothie in 25 seconds.
The plan justifying the unholy cost of this gadget is that our family will start consuming more fruits and vegetables because of this thing sitting on our kitchen counter.
My current fixation on fruits and vegetables stems from my current study project. I've been reading and then rereading a paper by Bharat Aggarwal from the MD Anderson Cancer Center in Texas and Shishir Shisodia of Texas Southern University, Aggarwal sums up what we know, well better said as, what they know, about how dietary agents work in cancer therapy. 
One of the most fascinating aspects of treating cancer using naturopathic therapies is watching the evolving science which supports our practices. The advancements in scientific understanding of the fine biochemical details of how dietary agents act in the last few years is mind boggling. Keep in mind that when I sat in my first biology class, professors were still in awe of Francis and Crick and the double helix, if no longer cutting edge, was still the high point of biological understanding.
The thing is that diet is probably the biggest arbiter in whether a person does or doesn't get cancer. People who migrate from a country that has a low per capita risk of getting cancer to a country with high risk, quickly assume the risk of people in their adopted country. At least they do, when they adopt the diet of their new country. An estimated 75-85% of all chronic diseases are linked to diet and lifestyle and cannot be explained by genetics. As exciting as the new technology that identifies genetic predispositions that increase odds of getting cancer, genetic cancers are in the minority. It's diet and lifestyle that usually decide, not genes.
Over the years, researchers keyed in to the idea that fruits and vegetables are important in preventing these chronic diseases and began to identify active chemical constituents that they felt were responsible for conferring protection against disease. These days the list of bioactive agents obtained from fruits and vegetables has grown quite long. The interesting part is that the list of molecular targets that these food agents act on has also grown in length and detail.
In my first draft of this newsletter, I included a very detailed list of the 16 most important chemical pathways and a list of which nutritional supplements effect these pathways to prevent or limit cancer growth. Having fallen asleep twice compiling this tedious list, I have decided not to bore you with all the details and will simplify it greatly. The bottom line here is what is important.
The bottom line is that the same few chemical compounds appear repeatedly over and over to effect each of the pathways on the lists. Curcumin appears most often, that is, it affects the greatest number of chemical pathways. Resveratrol, a chemical isolated from grapes and certain Chinese herbs (Polygonum cuspidatum in particular) came in second. Also near the top of the list are the catechins and flavonols from green tea, and then quercetin, and genistein. Of course, there are some odd little tidbits. The only target so far known to be effected by black raspberries are the serine/threonine protein kinase Akt/PKB, better known as cell survival kinase Akt.
For those of you who might like big words and their abbreviations, here is the basic list of 16 molecular targets of bioactive agents:
- Nuclear factor-kappa B (NF-kB)
- Activator protein-1 (AP-1)
- Cell Cycle
- Cell survival kinase Akt
- Tumor suppressor gene p-53
- Growth factor signaling pathways
- Chemokines and metastasis
- Tumor necrosis factor (TNF)
- Signal transducer and activator of transcription (STAT)
- Cyclooxygenase-2 (COX-2)
- Lipoxygenase (LOX)
- Inducible nitric oxide synthase (iNOS)
- Mitogen-activated protein (MAP) kinases
- DNA methylation
It is becoming ridiculously obvious that there are numerous agents found in fruits and vegetables that interfere with cell-signaling pathways in cancer cells. In their natural form in food, these chemicals can prevent cancer. In their purified forms, they can be used alone or in combination to treat cancer. In the concluding line of their paper's abstract, Aggarwal and Shishodia wrote, “ This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.”
Biochem Pharmacol. 2006 May 14;71(10):1397-421. Epub 2006 Feb 23.
Molecular targets of dietary agents for prevention and therapy of cancer.
Aggarwal BB , Shishodia S .
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA. firstname.lastname@example.org
While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.
PMID: 16563357 [PubMed - indexed for MEDLINE]
 Bharat Aggarwal and Shishir Shishodia. Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology 71 (2006) 1397-1421