Biomarkers of human colonic cell growth are influenced differently by a history of colonic neoplasia and the consumption of acarbose.
The nutritional effects of butyrate on the colonic mucosa and studies of transformed cells suggest that butyrate has anti-colon cancer effects. If butyrate has antineoplastic effects, mucosal growth contrasts between normal subjects and those with a history of colonic neoplasia would parallel changes in growth characteristics caused by butyrate in a colon neoplasia population. To test this hypothesis, rectal biopsies from a survey of colonoscopy patients (n = 50) with and without a history of colonic neoplasia (controls) were compared. Similarly, rectal biopsies were compared from subjects (n = 44) with a colon neoplasia history in an acarbose-placebo crossover trial. Control subjects in the colonoscopy survey had higher bromodeoxyuridine (BrdU) uptake than subjects with a history of neoplasia (P = 0.05). The control subjects also had a higher correlation of BrdU and Ki-67 labeling (P = 0.003). Both findings were paralleled by acarbose use. Acarbose augmented BrdU uptake (P = 0.0001) and improved the correlation of BrdU and Ki-67 labeling (P = 0.013). Acarbose also augmented fecal butyrate (P = 0.0001), which was positively correlated with Ki-67 labeling (P = 0.003). p52 antigen had an earlier pattern of crypt distribution in subjects with a history of colon neoplasia but was not affected by acarbose use. Lewis-Y antigen was expressed earlier in the crypt with acarbose but had similar expression in the colonoscopy survey groups. The use of acarbose to enhance fecal butyrate concentration produced mucosal changes paralleling the findings in control subjects as opposed to those with neoplasia, supporting the concept of an antineoplastic role for butyrate.
Weaver
G A
GA
Department of Medicine, Research Institute and. Department of Pathology, The Mary Imogene Bassett Hospital, Cooperstown, NY 13326, USA.
Tangel
C T
CT
Krause
J A
JA
Parfitt
M M
MM
Stragand
J J
JJ
Jenkins
P L
PL
Erb
T A
TA
Davidson
R H
RH
Alpern
H D
HD
Guiney
W B
WB
Higgins
P J
PJ
D020909:Acarbose / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000493:pharmacokinetics; D015415:Biomarkers; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002277:Carcinoma / Q000473:pathology / Q000517:prevention & control*; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D003113:Colonoscopy; D018592:Cross-Over Studies; D004032:Diet; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged
D000963:Antimetabolites; D015415:Biomarkers; D004791:Enzyme Inhibitors; D005232:Fatty Acids, Volatile; D019394:Ki-67 Antigen; D001973:Bromodeoxyuridine; D020909:Acarbose