Seems an age since I last read about nitric-oxide-donating NSAIDs & a possible anti-cancer effect.
First: is anyone using one?
From a 2005 paper on a nitric-oxide-donating aspirin [2]:
"Nitric-oxide-donating aspirin (NO-ASA), consisting of ASA (aspirin) plus an -ONO2 moiety linked to it via a molecular spacer, is a new drug for cancer prevention. NO-ASA seems to overcome the low potency and toxicity of traditional ASA. The -ONO2 moiety is responsible for releasing NO, and it appears to be required for biological activity. In studies in vitro, NO-ASA inhibits the growth of colon, pancreatic, prostate, lung, skin, leukaemia and breast cancer cells, and is up to 6000-fold more potent than traditional ASA."
Fourteen years later & we have another NO-aspirin cell study [1]:
"Non-steroidal anti-inflammatory drugs (NSAID) have shown promise as anticancer agents by inducing cell death apart from their antipyretic, anti-inflammatory and anti-thrombogenic effects. In our current study, we investigated the oxidative stress mediated cell death mechanism of a NSAID derivative NCX4040 (a nitric oxide releasing form of aspirin) in castration-resistant prostate cancer (CRPC) PC3 cell line. Our data revealed that NCX4040 is more potent than its parent compound aspirin or nitric oxide (NO) releasing compound DETA NONOate. NCX4040 significantly induced hydrogen peroxide formation with ensuing oxidative stress and mitochondrial depolarization resulting in lipid peroxidation, cell cycle arrest, inhibition of colony growth and induction of apoptosis in PC3 cells. Moreover, NCX4040 inhibited migration potential of PC3 cells ..."
The years fly by & I assumed that some NO-NSAIDs must have been approved by now. After all, they are supposed to be safer. But I don't see signs that the FDA has approved any. It didn't take this long for Zytiga & Xtandi!
I wonder if Nalakrats could throw together a NO-aspirin in his basement lab?
Since it's a safer aspirin, hard to believe it hasn't been approved..... criminal in my opinion, as I believe tens of thousands of people per year, at least, have bleeds from regular aspirin.
Description: NO-donating aspirin; anti-inflammatory and antitumor
Chemical Name: 2-(Acetyloxy)benzoic acid 4-[(nitrooxy)methyl]phenyl ester
Purity: ≥98% (HPLC)
Biological Activity
NO-donating aspirin; anti-inflammatory. Blocks inflammatory mediator production in isolated human monocytes (IC50 values are 0.07, 0.13, 0.15 and 0.18 μM for IL-1β, PGE2, IL-10 and TNF-α respectively). Decreases COX-2 expression (IC50 = 0.13 μM); disrupts proteasome-mediated degradation of iκB-α. Antiproliferative in HCT116 colon cancer cells; sensitizes drug-resistant ovarian tumor cells to cisplatin (Cat. No. 2251).
That's some pricey stuff. It's not clear what dose an individual pill provides or how many pills you get when you order a particular amount, or is this in powder form?
Tocris is a supplier of research grade chemicals and will not sell to individuals. This indicates that the drug has not been approved by the FDA. Maybe we should get into the drug manufacturing business Cheers, Phil
I am using L-Arginine, 1000 mg twice daily, which ends up as Nitric-oxide.
Nalakrats also recommended this in a higher dose 1000 mg three times daily.
There is another explanation as L Arginine potentiate T cells in the immune system.
In 1991, the University of Minnesota conducted one of the first studies to use l-arginine combined with omega-3 fatty acids and RNA. The study included 20 patients ages 31-80 from the ICU.
The researchers gave 11 patients a supplementation of 12.5 grams of l-arginine, 1.25 grams of RNA, and 11.1 grams of omega-3 fatty acids. The other 9 patients received a placebo. Each received their supplement for 7-10 days.
Those who took the l-arginine supplement had increased growth of T-cells, which aid the immune system to fight off infection, and also cancer!
"Melanoma, hepatocellular carcinoma, and prostate carcinoma were most frequently deficient in ASS" (Argininosuccinate synthetase). [1]
Which suggests that PCa might respond well to arginine depletion via ADI-PEG 20.
There has been a "Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors" - including PCa. [2]
"ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted, and expansion cohorts are now accruing for both castrate-resistant prostate cancer and non–small cell lung cancer at a recommended phase II dose of 36 mg/m2."
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Cheers, Phil
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SUPPORTING AND DONATING TO MALECARE.
