Calcipotriol inhibits rectal epithelial cell proliferation in ulcerative proctocolitis.
Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby protect against colorectal cancer. Cell turnover is increased in ulcerative proctocolitis, which might therefore respond to vitamin D3 metabolites. This study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis. Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M). After 15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest, and CCPR was determined by linear regression analysis of accumulated metaphases. Compared with values in 17 controls with incidental anal conditions, median rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80 (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22) cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition.
Thomas
M G
MG
Royal Postgraduate Medical School, Hammersmith Hospital, London.
Nugent
K P
KP
Forbes
A
A
Williamson
R C
RC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D003864:Depression, Chemical; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques
C055085:calcipotriene; D002117:Calcitriol