Polyphenols as Modulators of Oxidative Stress in Cancer
Reviewed by: Paul Anderson, NMD
Reference: Mileo AM and Miccadei S. Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies. Oxidative Medicine and Cellular Longevity. Volume 2016, Article ID 6475624, 17 pages. http://dx.doi.org/10.1155/2016/6475624
Design: Literature Review
Summary of findings:
I have been studying redox biology and immunology for the better part of three decades and the old adage “it’s not as easy as it looks” is so appropriate for the intersection of those two areas of medicine. This paper brings us up to date on the actions of polyphenols found in commonly prescribed natural supplements and foods in modulating redox biology in cancer. Although this paper is focused on cancer the data can be viewed in the larger context of any inflammatory condition.
The authors summarize their findings in the abstract in the following terms:
…many natural polyphenols have emerged as very promising anticancer bioactive compounds. Beside their well-known antioxidant activities, several polyphenols target epigenetic processes involved in cancer development through the modulation of oxidative stress. An alternative strategy to the cytotoxic treatment is an approach leading to cytostasis through the induction of therapy-induced senescence. Many anticancer polyphenols cause cellular growth arrest through the induction of a ROS-dependent premature senescence and are considered promising antitumour therapeutic tools. Furthermore, one of the most innovative and interesting topics is the evaluation of efficacy of prooxidant therapies on cancer stem cells (CSCs). Several ROS inducers-polyphenols can impact CSCs metabolisms and self-renewal related pathways.
To break this down into more finite clinical points we can look at the following mechanistic functions:
- Antioxidant properties:
I believe all the readers will be familiar with “antioxidant” properties and their importance so I will not summarize this mechanism.
- Epigenetic modulation via redox:
The authors summarize:
“..the role of natural polyphenols on modulating intracellular ROS levels leading to epigenetic modifications of pivotal genes in tumorigenesis. It is important to stress that DNA methylation and posttranslational histone modifications are crucial actors in epigenomic landscape playing a relevant role in the structure and function of chromatin. Several polyphenols were demonstrated to interfere with enzymes driving the epigenetic alterations which modulate inflammation process that might hesitate in cancer.”
Basically saying that a diet high in these polyphenols and appropriate additions via supplementation, can change the genomic landscape in a direction that opposes tumorigenesis.
- Reactive Oxygen Species (ROS) factors:
The authors describe the duality of ROS in the biology of cancer:
“Compared to normal cells, cancer cells have an increased rate of ROS production and have aberrant regulation mechanisms to deal with their particular redox status. ROS have a well-defined role in promoting and maintaining tumorigenicity indicating that dietary antioxidants have an active role in preventing or reducing tumorigenesis. On the other hand, high levels of ROS can also be toxic to neoplastic cells and can potentially induce cell death.” These polyphenols can actually in a dose dependent manner (much like ascorbic acid) manipulate the ROS in both directions of this duality.”
- ROS dependent tumor cell senescence:
Senescence is a concept long known but on the rise as a focus of tumor biology which is both a part of tumor suppression as well as the actual success of anti-cancer therapies. The authors summarize the potential for polyphenols and senescence in the following way: “prosenescence therapy, which could be an important alternative or addition to conventional chemo /radiotherapy.” To this aim, prosenescence-polyphenols treatment may minimize toxicity and side effects of conventional therapies in cancer patients.
- ROS mediated cancer stem cell manipulation:
The manipulation of cancer stem cells (or cancer stem-like cells a.k.a. CSCs) is another growing area of interest in tumor biology and cancer care. In sum the ability to decrease or eradicate tumor stem cells is required to stop tumor recurrence. The summary does an excellent job of encapsulating the crucial role of cancer stem cells in positive or negative outcomes in cancer:
“The association of cancer stem cells and the resistance to chemo-/radiotherapy stimulate a critical consideration regarding the efficiency of prooxidant therapy on CSCs. Most conventional anticancer therapies are ineffective in killing this cell population. It is for this reason that there has been a growing interest to develop new strategies based on identifying agents able to directly target quiescent cancer stem cells. Since low ROS levels has been suggested to be critical for maintaining cellular “stemness”, an increase of these reactive species polyphenol-mediated might sensitize cancer stem cells to therapy.”
It is clear standard therapies are not the current road to CSC control and polyphenols and other natural agents may be included in future therapies in this arena.
Some of the polyphenols reviewed in the study include:
- Isothiocyanates (broccoli, cabbage, Brussel sprouts and cauliflower)
- Pterostilbene (blueberry and like flavonoids)
- Sulphoraphane (broccoli, cabbage and kale)
The above list of food based polyphenols are common in recommendations for diet additions and supplements. While it is true that in some mechanisms discussed doses of the polyphenol may require additional supplementation beyond diet, it is also true that in the preventive setting this bolsters our existing ideas of preventing disease through diet. In my estimation the best medicine is built on the diet and then things like supplementation and other therapies have a better opportunity to perform at their best.
Beyond dietary changes, I believe this paper reinforces the benefits of many polyphenolic compounds we commonly prescribe in cancer and chronic illness. I believe the real benefit of reviews such as this (in addition to reinforcing our comfort with common natural therapies) is the evolution of our understanding of the multiple beneficial mechanisms of these powerful natural agents. With immunology and tumor biology searching for keys to cell senescence, tumor stem cell effects and other immune-therapeutics, it is exciting to see that many of our most common natural therapies and dietary interventions are actually already acting positively in those arenas.