I recently re-read a paper that was discussed in this forum over a year ago. I bring it up now because I have re-thought some of the supplements I presently take and plan to make changes in my regimen. The paper in question, “Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism, NPJ Precision Oncolog (2017) 1:18 ; doi:10.1038/s41698-017-0024-zy.”
On one level, the results of this study are very useful because it provides the names of the most effective plant-based supplements available.
“High-throughput screening of [142] natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were modulated to a greater extent by the combinations compared to the individual compounds. Overall, this approach can be useful for identifying synergistic combinations of natural compounds for chemopreventive and therapeutic interventions.”
The entire study is available with all of the details. The study reveals its failure on another level, namely the results are given in “uM”
HMVP2 cells were screened at three different concentrations (5, 10 and 20µM) and three time points (12, 24 and 48h). Z-factors were calculated to evaluate cell response (based on ATP suppression) following exposure to the natural compounds.
A Z-factor value greater than 0.5 was considered a very good response. The 20µM treatment resulted in the highest number of compounds with Z-factors greater than 0.5 and ATP values lower than 0.5 (indicating good suppression) and was therefore selected as the best dose for the selection of the top hits (Fig. 1, ATP only). ATP and the derived Z-factors for all treatments and all doses are included in Supplementary Table 1. ATP suppression in treated HMVP2 cells varied greatly, with the majority of the screened natural compounds inducing a moderate drop in ATP concentration to >50% of control (Fig. 1). Notably, after 12h of treatment at the 20µM dose, the majority of the natural compounds under study induced a greater suppression of ATP levels compared to untreated (solvent control) samples than longer treatments at the same dose.
The so-called “top hits” were Ursolic Acid, Curcumin, and Reservatrol. However, 20uM
refers to the screening of HMVP2 cells, how well or poorly they did with the combinations. It doesn't tell us the concentrations of these natural compounds fed to the mice. If someone out there can translate uM into mg/kg please do so. It is not easily converted because these are two different ways of measurement.
So, I called up the lab at which the study was done and asked to speak to the person who wrote the paper. I learned that she had moved on and was no longer employed there. The person with whom I spoke said she had taken that individual's place. I therefore asked her to answer the question. In turns out that she was unable to make such a conversion and that she had received other calls from “laypeople” asking similar questions. The answer she was told to give us is “take a copy of the paper to your physician to discuss with him.” At this point I became a little difficult: I told her that although I realize the paper was written for peers, nevertheless, it was irresponsible to publish such results. How does the reader not know that these mice were given hundreds of grams to obtain these results? If true, then there is no way in the world that someone could even attempt to mimic the therapeutic amounts fed to the mice. She finally agreed to speak with the researchers and get back to me.
Meanwhile, we learn that there is an on-going trial of curcumin at 500x2 (See cesanon) . If this is an effective dose, the paper in question reveals that a combination of the three winners is more effective than single doses of one supplement. It would be a good starting point.
Natural Vit E and Prevention
New hope for survival prostate cancer with curcumin
