Allopurinol

[Graham49]

I was prescribed Allopurinol for gout and searched the Internet for its effect on prostate cancer. See abstracts from two papers below.

Mol Cancer Res. 2008 Dec;6(12):1852-60. doi: 10.1158/1541-7786.MCR-08-0012.

Anti-gout agent allopurinol exerts cytotoxicity to human hormone-refractory prostate cancer cells in combination with tumor necrosis factor-related apoptosis-inducing ligand.

Yasuda T1, Yoshida T, Goda AE, Horinaka M, Yano K, Shiraishi T, Wakada M, Mizutani Y, Miki T, Sakai T.

Abstract

Allopurinol has been used for the treatment of gout and conditions associated with hyperuricemia for several decades. We explored the potential of allopurinol on cancer treatment. Allopurinol did not expose cytotoxicity as a single treatment in human hormone refractory prostate cancer cell lines, PC-3 and DU145. However, allopurinol drastically induced apoptosis of PC-3 and DU145 in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is a promising candidate for anticancer agent but its efficacy is limited by the existence of resistant cancer cells. We examined the underlying mechanism by which allopurinol overcomes the resistance of prostate cancer cells to TRAIL. Allopurinol up-regulated the expression of a proapoptotic TRAIL receptor, death receptor 5 (DR5). Allopurinol increased DR5 protein, mRNA, and promoter activity. Using DR5 small interfering RNA (siRNA), we showed that allopurinol-mediated DR5 up-regulation contributed to the enhancement of TRAIL effect by allopurinol. Furthermore, we examined the mechanism of allopurinol-mediated DR5 up-regulation. DR5 promoter activity induced by allopurinol was diminished by a mutation of a CAAT/enhancer binding protein homologous protein (CHOP)-binding site. In addition, allopurinol also increased CHOP expression, suggesting that allopurinol induced DR5 expression via CHOP. Allopurinol possesses the activity of a xanthine oxidase (XO) inhibitor. We used XO siRNA instead of allopurinol. XO siRNA also up-regulated DR5 and CHOP expression and sensitized the prostate cancer cells to TRAIL-induced apoptosis. Here, we show the novel potential of allopurinol in cancer treatment and indicate that the combination of allopurinol with TRAIL is effective strategy to expand the TRAIL-mediated cancer therapy.

PMID: 19074830 DOI: 10.1158/1541-7786.MCR-08-0012Mol Cancer Res. 2008 Dec;6(12):1852-60. doi: 10.1158/1541-7786.MCR-08-0012.

CR-08-0012

Prostate Cancer Prostatic Dis. 2017 Sep;20(3):328-333. doi: 10.1038/pcan.2017.14. Epub 2017 Apr 11.

Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study.

Shih HJ1,2,3, Kao MC4,5, Tsai PS6, Fan YC4, Huang CJ4,5.

Abstract

BACKGROUND:

Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients.

METHODS:

We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders.

RESULTS:

A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019).

CONCLUSIONS:

Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

PMID: 28398294 DOI: 10.1038/pcan.2017.14

[Indexed for MEDLINE]

[adlerman]

Allopurinol in my experience is used to prevent gout while colcachine is used to treat outbreaks of gout. I've only needed colcachine twice in over 15 years. Allopurinol keeps the uric acid level in the normal range. Colcachine in my experience has not been needed beyond 2-3 days to get the uric acid level back in the normal range.

[Graham49 in reply to adlerman]

I note that Colchicine also appears to have anti cancer properties, see paper below.

Wolters Kluwer Health

Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

A 12-Year Cohort Study

Ming-Chun Kuo, MD, Shun-Jen Chang, PhD, and Ming-Chia Hsieh, MD, PhD

Additional article information

Abstract

Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout.