Ashwagandha is an adaptogen (one of those mysterious herbs that are claimed to restore homeostasis). Better known for its effects on thyroid balance & cortisol control, there have also been some prostate studies.
Ashwagandha has a long history of use in Ayurvedic medicine.
"The leaves contain the steroidal lactones, withanolides, notably withaferin A {WA}..." [1a] [1b]
"Ashwagandha include three natural powerful antioxidants-superoxide dismutase, catalase and glutathione peroxidase ..." [3]
[2] (2007 - U.S.)
"Our findings suggest that WA preferentially induces apoptosis in androgen-refractory prostate cancer cells but not in androgen-responsive (WT AR or AR mutant) prostate cancer cells and normal/immortalized prostate epithelial cells. Interestingly, treatment of androgen-responsive prostate cancer cells with anti-androgens (flutamide and Casodex; data not shown), which on their own do not cause apoptosis, rendered the cells amenable to apoptosis by WA."
[3] (2008/2010 - U.S.)
"Ashwagandha treatment significantly downregulated the gene and protein expression of proinflammatory cytokines ..."
"Furthermore, Ashwagandha treatment significantly modulated the JAK-STAT pathway which regulates ... the apoptosis process ..."
"Stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of attention as a putative target for tumor therapy since it is an important regulator of cancer cell growth. Expression of Hsp70 in tumor cells has been proposed to enhance their immunogenicity and prevent tumor cell death. Ashwagandha treatment significantly decreases the gene and protein expression of Hsp70, which may result in the generation of a specific immune response by promoting apoptosis."
"Our results showed that Ashwagandha treatment modulated several functionally important classes of genes, which are associated with cell cycle regulation, regulation of apoptosis, modulation of stress proteins, cytokine and chemokine regulation, regulation of signal transduction, and oncogene regulation in prostate cancer cells (PC-3)."
[4] (2014 - U.S.)
"Withaferin-A induces mitotic catastrophe and growth arrest in prostate cancer cells."
"Cell cycle deregulation is strongly associated with the pathogenesis of prostate cancer (CaP). Clinical trials of cell cycle regulators that target either the G0/G1 or G2/M phase to inhibit the growth of cancers including CaP are increasing."
"WA induced irreversible G2/M arrest in both CaP cell lines (PC3 and DU145) for 48 h."
[5] (2015 - Japan)
"Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells."
"We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts ..."
...
Studies [2] & [5], using the old terms "androgen-refractory" & "androgen-Independent", report that ashwagandha preferentially acts on CRPC cells. No explanation why this might be so, except perhaps that normal funtioning androgen receptors might resist the herb. Further, [2] reports synergy with Casodex, so it might work well with Xtandi.
{As with almost all natural products, there have been no PCa clinical trials.}
-Patrick
[1a] en.wikipedia.org/wiki/Witha...
[1b] en.wikipedia.org/wiki/Witha...
[2] cancerres.aacrjournals.org/...
[3] ncbi.nlm.nih.gov/pmc/articl...
[4] ncbi.nlm.nih.gov/pmc/articl...
[5] ncbi.nlm.nih.gov/pmc/articl...
Bipolar Androgen Therapy (BAT) and CRPC
