By now, you will have had your fill of the study conducted by Dr. Pier Paolo Pandolfi [1], but keep reading.
To summarize the mice findings:
i) PCa cells that had lost PTEN and PML turned into fat-producing machines & became metastatic.
ii) PCa cells that had lost PTEN but not PML were indolent.
iii) When mice with indolent cells were fed a high saturated fat Western diet, the PCa became metastatic.
iv) Media message: high-fat diets cause fatal PCa.
However: “You cannot just say, ‘Don’t eat fat,'” Pandolfi said. [New York Times]
In fact, Pandolfi's interest is now in Fatostatin, which prevents the creation of fat.
...
It has been known for at least 20 years that aggressive PCa cells manufacture fat. This has nothing to do with diet.
"... increased de novo lipid synthesis ... is an early event of the disease. Up-regulation and increased activity of lipogenic enzymes (including fatty acid synthase and choline kinase) occurs throughout PCa carcinogenesis and correlates with worse prognosis and poor survival." [2]
Note: Fatty Acid Synthase [FAS] is an enzyme (encoded by the FASN gene) that is used in the synthesis of fatty acids (lipids).
"Overexpression of FASN is an early event in PCa pathogenesis, associated with PCa progression and metastases to the bone. Elevated expression of FASN has been linked with poor prognosis and reduced disease-free survival in PCa" [2]
"The major transcriptional regulator of the lipogenic enzymes ... is the sterol response element binding protein-1 (SREBP-1). Expression of SREBP-1 can be stimulated by androgens and epidermal growth factor (EGF) in PCa, and in turn, expression of the androgen receptor is regulated by SREBP-1, creating a positive feedback loop for the expression of lipogenic enzymes. Moreover, overexpression of SREBP-1 is sufficient to increase tumorigenicity and invasion of PCa." [2]
This is old news. i.e. the generally accepted view is that aggressive PCa must make the lipids required for proliferation. We could interfere with that by targeting FASN or SREBP-1. Fatostatin inhibits SREBP-1.
[3] (2011) "Inhibition of SREBP1 sensitizes cells to death ligands"
[4] (2014) "Fatostatin Displays High Anti-Tumor Activity in Prostate Cancer by Blocking SREBP-Regulated Metabolic Pathways and Androgen Receptor Signaling"
[5] (2014) "Silibinin inhibits aberrant lipid metabolism, proliferation and emergence of androgen-independence in prostate cancer cells via primarily targeting the sterol response element binding protein 1"
"The importance of lipids in cancer progression was established after several studies showing that normal cells ... meet their requirement of lipids through uptake of free fatty acids from the diet; however, in case of cancer cells, more than 90% of their elevated lipid needs, are fulfilled by de novo lipogenesis."
That puts dietary fat in perspective.
"... the expression of master transcriptional regulator of lipid synthesis enzymes, sterol regulatory element binding protein 1 (SREBP1), is strongly correlated with Gleason grade. SREBP1 overexpression alone is sufficient to increase tumorigenicity and invasiveness of PCA cells, while its inhibition decreases de novo fatty acid synthesis and causes PCA growth inhibition and apoptosis induction."
"Results from present study showed that silibinin effectively decreases SREBP1 expression through AMPK activation in PCA cells, and that silibinin-mediated SREBP1 inhibition is critical for its anti-cancer efficacy against PCA."
...
Milk Thistle has been used for centuries for liver health. The literature can be confusing, since there are a number of active components. The better products are standardized - usually to 80% silymarin, where silibinin is the primary fraction. Silibinin itself is made up of silybin A and silybin B.
-Patrick
[1] iol.co.za/lifestyle/health/...
[2] ncbi.nlm.nih.gov/pmc/articl...
[3] ncbi.nlm.nih.gov/pmc/articl...
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