Foods/Supplements-Vitamins: Curcumin - Advanced Prostate...

Advanced Prostate Cancer

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Foods/Supplements-Vitamins: Curcumin

8 years ago•4 Replies

This is a daunting subject - 272 hits on PubMed for <prostate curcumin>. Only 92 for <prostate[title] curcumin[title]>, so I will confine this post to them.

Curcumin (Diferuloylmethane) is the main active component of turmeric (from the rhizome of curcuma longa), a root "spice" used in many Indian dishes. I don't really view it as a spice, since it is used sparingly in Indian recipes & has little effect on the dominant flavors of any dish I have tasted. Personally, given the long history of turmeric in Ayurvedic medicine, I feel that it is included in dishes for digestive reasons & it is also known to stimulate the appetite. (Another spice used widely in Indian cuisine - although not in the westernized versions - is asafoetida, a recognized digestive aid, so it isn't off the wall to view turmeric that way.)

In spite of the traditional medicinal use of turmeric, curcumin is considered to have poor bioavailability in the context of cancer treatment. Life Extension's "Super Bio-Curcumin" [Product-1] can only boast a bioavailability factor of 7, compared to the least useful form.

Turmeric is dirt-cheap in Indian grocery stores. Even at Penzeys [Product-2], 3 cups of the stuff cost under $15. One might do better to learn to like turmeric tea (very popular in some quarters), than to use the relatively expensive LEF product.

At the other end of bioavailability, Anthony Loera of RevGenetics (Dr. Myers recommends his micronized resveratrol) offers MetaCurcumin [Product-3]. Looks like he claims a bioavailability factor of 200. It may be high-end pricewise, but comparing prices based on an effective plasma target dose is the only way to properly compare curcumin products. In addition, Anthony's credibility is in no small part due to his quality control procedures - always a concern with supplements.

Having said that, I currently use CurcuBrain [Product-4a] The real name is Longvida®. The reason I use it is because of a study [Product-4b] that gives compelling evidence of bioavailability - if it can get to the brain, perhaps it can get to PCa cells? Of course, one has to be comfortable with it getting to the brain!

"Longvida® Optimized Curcumin is a breakthrough formula of the natural antioxidant curcumin, from the turmeric root. It is optimized to deliver free curcumin into target tissues through the critical bioavailability requirements of permeability, solubility, and stability. Developed in collaboration with elite neuroscientists at UCLA, Longvida® carries a strong safety profile and is self-GRAS." [Product-4c]

ANALOGS.

In parallel with efforts to increase bioavailability, there are numerous efforts to create analogs with increased bioavailabilty & efficacy. Those folks might have already lost the race, but the smart money is on curcumin, in some form, having a role in PCa treatment. While the scope of the effort is of interest, it wouldn't be information we could use right now, so no studies are cited.

STUDIES.

[1] Epigenetics.

One of my favorite topics, since it makes me hopeful that epigenetic changes, by virtue of existing above the gene level, represent the Achilles heel of cancer. Curcumin is one of a small number of polyphenols that have demonstrated an ability to roll back epigenetic changes.

[1a] Perhaps appropriate to begin with an Indian study (2016). It's an odd one though, since the current view of CRPC is that the androgen receptor [AR] continues to drive progression. In this study, AR-negative PCa cells were restored to express AR, thereby making them sensitive to anti-androgen treatment. The interesting idea, though, is that curcumin, with quercetin, is able to reverse epigenetic silencing. Many beneficial genes are silenced in an epigenetic way.

[1b] A 2007 cell study:

"Acetylation of histone H3 and H4 was increased in cells treated with curcumin, suggesting histone modification may regulate gene expression."

[1c] A 2011 cell study. The following will read like a foreign language, but it's good news:

"CUR has been found to inhibit histone acetyltransferase activity, and it was also postulated to be a potential DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitor. In this study, we show that when human prostate LNCaP cells were treated with CUR, it led to demethylation of the first 14 CpG sites of the CpG island of the Neurog1 gene and restored the expression of this cancer-related CpG-methylation epigenome marker gene."

"... our present study provides evidence on the CpG demethylation ability of CUR on Neurog1 while activating its expression, suggesting a potential epigenetic modifying role for this phytochemical compound in human prostate cancer cells."

PCa cells tend to be hypermethylated. Further, certain DNA regions that are never methylated in normal cells (the CpG islands in charge of tumor-suppressor genes) are invariably methylated, i.e. silenced. If curcumin is an effective demethylation agent, that would be a very good thing.

[2] Drug Resistance.

Adding a polyphenol such as curcumin to a standard drug treatment in order to combat drug resistance is something that patients might attempt. In PCa treatments, we know that the mean time to failure is mostly disappointingly short, compared to one's life expectancy from actuarial tables.

I think it would be smart for drug companies to look for simple fixes to the drug resistance that limits the life of their big money earners.

[2a] (2016 - France) Curcumin added to Docetaxel+Prednisone in CRPC. A Pilot Phase II Study. "... docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel)."

"Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant."

[2b] (2016 - China) Interesting mouse study combining Docetaxel & curcumin in nanoparticles, but not immediately useful.

Rationale: "Combination anticancer therapy encapsulating {Docetaxel} and {an} extract of traditional Chinese medicine in one nano-sized drug delivery system promising to generate synergistic anticancer effects, to maximize the treatment effect, and to overcome multi-drug resistance."

[2c] (2015 - China) Cell study using curcumin with Casodex.

"We showed that curcumin inhibited the growth of androgen-independent prostate cancer cells and a synergy was observed in the presence of curcumin and bicalutamide, the androgen receptor antagonist."

[3] Radioresistance.

Similar to drug resistance. Cancer cells don't want to be killed. The escape pathways are well-known.

[3a] 2004 cell study (p53 mutant prostate cancer cell line PC-3).

"... strongly suggest that the natural compound curcumin is a potent radiosesitizer, and it acts by overcoming the effects of radiation-induced prosurvival gene expression in prostate cancer."

[3b] (2016 - Iran) "Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients"

"In {the curcumin group}, {total antioxidant capacity} significantly increased ... and the activity of {superoxide dismutase} decreased ... after radiotherapy compared with those at baseline. In {the curcumin group}, however, the activity of {superoxide dismutase} had a significant reduction ... and {total antioxidant capacity} had a significant increase (P = 0.014) compared with those in {the placebo group}."

I don't know what they were aiming for, but the case for phytochemicals in radiation is to counter radioresistance. Only long-term follow-up will tell if there was benefit. ["3 mo after treatment ... no significant differences were observed between the 2 groups regarding treatment outcomes"]

[4] Cell Line Studies.

The next group of studies used the popular cell lines LNCaP (derived from lymph node PCa), PC-3 (derived from bone mets) & DU145 (derived from brain mets).

Some of these studies included cells injected into mice.

The topics that I looked for were cell death (apoptosis), halting of the cell cycle (a dividing cell has to go through a series of phases before it becomes two cells. Curcumin can halt the process), inhibition of angiogenesis (formation of new blood vessels), down-regulation of the androgen receptor [AR], PSA reduction & invasiveness.

-cell death [4a] [4c] [4f] [4g] [4k] [4m]

-cell cycle arrest [4g] [4k]

-angiogenesis [4a] [4g]

-androgen receptor [4b] [4h]

-PSA [4d]

-invasiveness/metastasis [4e] [4i] [4j] [4l]

[5] Cell signalling pathway studies.

Many of the studies are concerned with cancer-induced cell changes that are inhibited by curcumin.

-EGFR [5a]

-NF-kB [5b] [5d] [5e] [5f]

-Akt [5c] [5e] [1b]

-VEGF [5g]