Possible repurposing of anti gout drugs for PCa

[Graham49]

There have previously been observational studies showing reduced PCa among users of the anti gout drug allopurinol. Here is a recent study that might explain the observational results.

Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue

by Andrej Veljković 1,*OrcID, Jovan Hadži-Dokić 2, Dušan Sokolović 1OrcID, Dragoslav Bašić 3, Ljubinka Veličković-Janković 3, Marko Stojanović 3, Dejan Popović 3 and Gordana Kocić 1

1 Faculty of Medicine, University of Niš, 18 000 Niš, Serbia

2 Serbian Academy of Sciences and Arts, 11 000 Belgrade, Serbia

3 Clinical Center, 18000 Niš, Serbia

*Author to whom correspondence should be addressed.

Diagnostics 2020, 10(9), 668; doi.org/10.3390/diagnostics...

Received: 30 June 2020 / Revised: 9 August 2020 / Accepted: 28 August 2020 / Published: 3 September 2020

(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)

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Abstract

Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy. View Full-Text

[LearnAll]

Thanks for this new study. It means if we block xanthine oxidase enzyme, we can block another pathway of inflammation and that can slow growth of prostate cancer cells. Allopurinol is a medicine for Gout which does it. But, many dietary substances can also block Xanthine Oxidase...Some are:

(1) Ellagic Acid in Pomegranade peel powder.

(2) Caffeic Acid in Pippali (long pepper)

(3) Phytic Acid in Legumes

(4) Flavonoids like Apigenin, Quercetin, Genistein etc.

(5) Cinnamondehyde from Cinnamon spice,

(6) Powder of dried mature papaya leaves.

(7) Rosemaric acid from RoseMary spice.

And Lastly, the most interesting one...petals of Chrysanthemum flowers.

You can pick 2 or 3 from above list and you will not need a prescription for Allopurinol.

[LearnAll in reply to LearnAll]

ncbi.nlm.nih.gov/pmc/articl...

Some people on this forum have written in past that eating lots of anti oxidant foods and supplements can protect cancer cells from dying. This is totally wrong impression.

Actually, we need to have a lot of anti oxidants to counter damage to cells and to stop them from converting into cancer cells. Note the findings of above study.

[LearnAll]

There is conflicting information about Uric acid. Some studies say Uric Acid works like anti oxidants ..whereas others say excessive Uric Acid makes cancer cells grow faster. Confusing.But there is a correlation between LOW uric acid and presence of prostate Cancer. The explanation given is that because uric acid acts like anti oxidant, the body utilizes it to thwart cancer growth...and hence. .the serum uric level is found low in active prostate cancer.

I am still not clear what we can accomplish by further lowering of Serum Uric acid by allopurinol ?

[Graham49 in reply to LearnAll]

Please see the paper below. It throws some light on lowering serum uric acid. If you lower your serum uric acid to 6 mg/dL, this is great, no need for allopurinol.

[pjoshea13]

Hi Graham,

Old post (4 years ago - some members who have gone silent):

healthunlocked.com/advanced....

-Patrick

[Graham49 in reply to pjoshea13]

Thanks for your reply Patrick. It spurred me on to search for a paper that summarized current scientific understanding of hyperuricemia and drugs that lower serum uric acid levels in relation to cancer. The full review paper is available on Google Scholar. It turns out that hyperuricemia is implicated in many cancers but normal uric acid levels are anti-oxidant and protective.

J Cancer. 2020; 11(17): 5236-5244. doi: 10.7150/ica

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Shuyi Mi, Liang Gong, and Ziqi Sui

Additional article information

Abstract

In recent years, metabolic syndrome (Mets) has been a hot topic among medical scientists. Mets has an intimate relationship with the incidence and development of various cancers. As a contributory factor of Mets, hyperuricemia actually plays an inseparable role in the formation of various metabolic disorders. Although uric acid is classically considered an antioxidant with beneficial effects, mounting evidence indicates that a high serum uric acid (SUA) level may serve as a pro-oxidant to generate inflammatory reactions and oxidative stress. In this review, we describe the unrecognized role of hyperuricemia in cancer development and summarize major mechanisms linking uric acid to carcinogenesis. Furthermore, we also discuss the potential mechanism of liver metastasis of cancer and list some types of uric acid-lowering agents, which may exert anticancer effects.

In summary, this review examines the novel idea that uric acid may be an important risk factor for cancer when humans develop a high concentration of SUA. Hyperuricemia may also contribute to the metastasis of some cancers, but the precise mechanism still needs further exploration. We also suggest a new target that may integrate inflammation, oxidative stress, and cell cycle arrest, which have been largely neglected, but are known to be responsive to drug treatment. Based on preliminary clinical evidence, we suggest that drugs that lower serum uric acid might be useful to slow or delay the progression of cancer development. But the specific or approximate extent to which lowering uric acid remains unclear, and recently a cohort study has suggested that an SUA level of 5.7 mg/dL (6mg/dL in males and 4mg/dL in females) is considered safe with respect to mortality. Repurposing these existing drugs may therefore be a novel strategy for management of some refractory cancers, but the application of those drugs needs further analyses.n

[Currumpaw]

Hey Graham49!

Imagine that! About 15 years ago while in the market a short woman asked me if I would get her a can of dark cherries on the top shelf. Of course! She asked for a second can and a third telling me to "keep them coming, I'll say when!". I couldn't help but ask if she was making a pie or pies and that maybe these dark cherries might not be the best for a pie. She then educated me! Her husband has gout. The side effects from the medicines are uncomfortable for him. He has found that eating a can of these dark cherries is as effective as the medication and he avoids the side effects.

Currumpaw

[j-o-h-n in reply to Currumpaw]

She was pulling your leg.... her husband was using them in his manhattans.....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 11/26/2020 5:38 PM EST - HTD

[Graham49 in reply to Currumpaw]

Thanks Currumpaw. I drink cherry juice and it just about keeps my gout at bay but at 7.9 it is still too high. I am going to ask for a drug to lower it to about 6.