Dear Osa friends,
This week we’re saluting the end of Men’s Health Month with a discussion of research involving a particular phytonutrient which holds promise for mitigation of prostate cancer growth. Enjoy!
Fisetin and Prostate Cancer
Lycopene, a carotenoid found in high quantities in cooked tomato, is perhaps the best known chemoprotective plant compound in regard to prostate cancer. However, in keeping with the meandering and exploratory energy of summer, today we’re going to discuss some interesting research on a compound you likely have not previously heard of: fisetin.
But first, some quick background information on prostate cancer:
Prostate cancer is second only to skin malignancies in its prevalence among cancers affecting men, and it primarily affects men over the age of 65. When we think about the multitude of factors impacting the development of cancer, age is at the top of the list. One reason for this is that as we age, our cells can begin to change how they behave. In terms of cancer, two crucial behaviors that they lose control of are the abilities to appropriately die and to regulate gene expression. Two mechanisms by which cells lose these abilities are senescence, which is characterized by profound DNA damage, pro-inflammatory secretions, and resistance to normal cell death; and aberrant DNA methylation, which adversely affects the expression of genes that control cell growth and replication. Senescent cells are strongly associated with age-related diseases including cancer. While age may sound like something we do not have any control over, emerging research is revealing many different mechanisms by which plant compounds impact the functioning of our cells and can actually reverse age-related dysfunction.
Fisetin is a lesser-known polyphenol which has been studied primarily for its effects on cellular senescence related to prostate and other cancers.
In a 2018 study¹, one group of researchers found that, among plant polyphenols tested in cell cultures and in vivo in mice, fisetin had the most potent effect in regard to destroying dysfunctional cells. This ability is termed “senolysis,” a combination of the word “senescence” and the suffix “-lytic,” which means to destroy. A compound which is senolytic is that which can induce death in senescent cells.
Now, if you’ve been reading these newsletters long enough, you know that nothing that the body does is inherently good or bad, and senescence is no exception. That is to say, not all senescent cells may be considered deleterious. However, senolytic agents can be helpful in conditions when senescence is out of balance, such as in cancer and possibly aging in general. (If the concept of senolysis is particularly interesting to you, here is a NIH article on this growing field of research).
Fisetin has also been shown in other pre-clinical trials to enhance the effectiveness of chemotherapeutic agents, which means it may be useful as an adjunctive treatment. For example, a study² utilizing human prostate cancer cells demonstrated that fisetin interrupted the signaling pathways (mTOR and others) by which these cancer cells replicate.
These types of studies, in which a substance is tested in cells and/or in animals, are called pre-clinical because we do not yet have evidence from a randomized controlled trial conducted in humans. This is the case for many plant compounds, of course, largely due to the cost of conducting a clinical trial and the potential profitability of the substance itself (which, for most plant compounds, is very low or nonexistent). Pre-clinical evidence cannot be utilized as specifically or as assertively as human trial evidence; for example, we do not have a reliable dose of fisetin which is known to have a specific benefit. However, what we can do is use this information to improve our dietary choices for either primary or secondary prevention of disease. Using food is a reliably safe and effective way to get beneficial phytonutrients into our bodies.
Luckily, fisetin is found in a delicious array of fruits and vegetables including apples, persimmons, grapes, kiwis, onions, cucumbers and strawberries. Strawberries, grapes, cucumbers, and kiwis can all be enjoyed seasonally in the summer, persimmons in the fall, and onions in the winter, or year-round. Please note that strawberries, grapes, and apples are all on the Environmental Working Group’s “dirty dozen” list for 2024, so choose organic as often as you are able. Of course, please also listen to your body and avoid any foods to which you have a sensitivity.
I hope that the wandering energy of summer is taking you in new and exciting directions, with your eating and otherwise! Please watch for upcoming information on my fall group programs. If you are enjoying the newsletters, please help me grow my subscriber list by telling a friend and subscribing at the bottom of this page. And if you have any questions or topics of interest, reach out and let me know!
Warmly,
References
- Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y. Y., Melos, K. I., Pirtskhalava, T., Inman, C. L., McGuckian, C., Wade, E. A., Kato, J. I., Grassi, D., Wentworth, M., Burd, C. E., Arriaga, E. A., Ladiges, W. L., Tchkonia, T., Kirkland, J. L., … Niedernhofer, L. J. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18–28. https://doi.org/10.1016/j.ebiom.2018.09.015 https://pubmed.ncbi.nlm.nih.gov/30279143/
- Suh, Y., Afaq, F., Khan, N., Johnson, J. J., Khusro, F. H., & Mukhtar, H. (2010). Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis, 31(8), 1424–1433. https://doi.org/10.1093/carcin/bgq115 https://pubmed.ncbi.nlm.nih.gov/20530556/