Monday, January 21, 2013

Do Antioxidants Block Cancer Treatment?

     This blog is based on a suppositional paper written by Dr. James Watson, of DNA fame, and published in Open Biology. He argues that the presence of antioxidants in cancer cells blocks anticancer treatments. The only clinical evidence of which I am aware that supports his thesis is the study of Finnish male smokers which showed that those who took antioxidant supplements had a higher incidence of lung cancer, and there also are several studies of cancer cells in vitro that seem to demonstrate a similar effect of antioxidants.

     Dr. Watson's paper is long and highly technical, so I will summarize the key points here and try to interpret them for the reader who is not heavily involved in cancer research. I might just begin by remarking that no interventional diet study involving the addition of antioxidants to the daily diet (beta carotene, Vitamin E, selenium, Vitamin A, and Vitamin C) has been shown to prolong the human life span. I will also touch on the possible reason for the benefit of aspirin in cancer prevention and why tests are now being done to see if the diabetes drug metformin has anti-cancer properties.

     Most agents used to kill organ (non bone-marrow) cancers, including Xrays and chemotherapy, work by generating ROS, or reactive oxygen species (such as OH-) which block key steps in the cell cycle and thereby hasten apoptosis, or cell self-destruction. The presence of ROS also generates a hypoxic environment in the cell, which drives a conversion of the cell from an epithelial to a mesenchymal type. But at the same time, in self-protection, the presence of ROS causes the cell to generate antioxidants, which render the cell resistant if not immune to both ionizing radiation and chemotherapy. In addition, mesenchymal cells are more prone to travel and metastasize. So the presence of ROS is both an accelerator and a brake.

     The presence of the Myc gene  activator can drive cancer cells forward, as can the presence of inflammatory cytokines such as interleukin-6. It is therefore theorized than the cancer-preventing property of daily aspirin (most convincingly demonstrated in colon cancer) derives from its anti-inflammatory and cytokine suppressing effect. And it has been shown that the turning off of Myc drives cancer cells towards apoptosis.

     Now in mouse models of cancer, the anti-diabetic drug metformin preferentially killed mesenchymal stem cells, which cells are the most resistant to chemotherapy and the most prone to metastasize. The reason for this is probably its blocking of oxidative phosphorylation. There are currently a number of ongoing studies where metformin is being added to standard anticancer chemotherapies in humans to look for an enhanced killing effect.

     To summarize Dr. Watson's thesis, and again I refer the interested reader to his paper, anticancer chemotherapy and Xrays generate ROS. The presence of ROS has a two-fold effect: it drives the cancer cell  towards apoptosis, or cell death, and at the same time it induces antioxidants which render the cell resistant to further anticancer treatment as well as inducing a transformation to a mesenchymal stem cell. It is not known if the antioxidants themselves drive this change in addition to inducing resistance to treatment.

     Based on this theory, and the limited data to date, it would seem prudent to avoid adding antioxidants to your diet which in theory would increase the antioxidant levels in every cell in your body by diffusion. Remember the study of Vitamin E, touted as an oxidant, which showed (in two different studies) that an increase in the intake of Vitamin E increased the rate of cardiac events and heart attacks.





1 comment:

  1. Hi,
    I am the producer of MD Anderson Cancer Center's audio podcast series called Cancer Newsline. Recently we published an episode on how medical hypnosis may help the cancer patient. I thought you and your readers may be interested in it. Feel free to embed in a post!