Antiproliferative effect of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on colonic epithelium of patients with adenomatous polyps in vitro.
We have consistently shown that the organoselenium compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a superior cancer chemopreventive agent and less toxic than selenite or certain naturally-occurring selenoamino acids. To elucidate the effects of p-XSC on human colonic mucosa, biopsies from endoscopically normal sigmoid colon of 30 patients with adenomatous polyps were incubated with p-XSC at concentrations of 1, 2 and 5 micromol/l dissolved in dimethylsulphoxide (DMSO). Biopsies incubated with DMSO or pure culture medium served as a control. Proliferating cells were labelled by bromodeoxyuridine immunohistochemistry and the labelling index (LI) was computed. Upper crypt labelling index (LI of crypt compartments 4+5) and Phih value, which are both discriminators of the expansion of the proliferative zone, were significantly lower after incubation with 1 and 5 micromol/l p-XSC, respectively (LI 4+5: 0.8 and 1.0; Phih value: 2.1 and 2.4), as compared with DMSO (LI 4+5: 3.6 and 4.5; Phih value: 7.0 and 8.3) or culture medium (LI 4+5: 3.3 and 4.5; Phih value: 7.2 and 8.1) (P<0.005 and P<0.05 by Friedman's block test). A trend towards lower levels of LI 4+5 (P=0.059) and Phih value (P=0.075) were seen after 2 micromol/l p-XSC incubation compared with DMSO. Since hyperproliferation of colonic crypt cells with expansion of the proliferative zone is regarded as a biomarker of increased cancer risk, the antiproliferative effects of p-XSC especially on upper crypt LI and Phih value may indicate a possible protective effect of this organoselenium compound in the prevention of human colon cancer development.
Bartram
H-P
HP
Gastroenterological Practice, Bahnhofstr. 29, 86150 Augsburg, Germany. HP.Bartram@t-online.de
Krüger
S
S
Dusel
G
G
El-Bayoumy
K
K
Upadhyaya
P
P
Scheppach
W
W
D018256:Adenomatous Polyps / Q000473:pathology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D018929:Cell Culture Techniques; D002455:Cell Division; D003106:Colon / Q000166:cytology* / Q000187:drug effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D012307:Risk Factors
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D016566:Organoselenium Compounds; C074153:1,4-phenylenebis(methylene)selenocyanate