Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats.
Prebiotics such as fructans, and probiotics such as Lactobacilli or Bifidobacteria, or a combination of prebiotics and probiotics (synbiotics) are thought to be protective against colon cancer. Therefore, we studied whether the prebiotic inulin enriched with oligofructose (Raftilose-Synergy1, briefly, Synergy1, 10% of the diet), probiotics [Bifidobacterium lactis (Bb12) and Lactobacillus rhamnosus (LGG), each at 5x10(8) c.f.u./g diet] or synbiotics (a combination of the two) protect rats against azoxymethane (AOM)-induced colon cancer. Male F344 rats were divided into: Controls; PRE, which were fed a diet containing Synergy1; PRO, fed a diet containing LGG and Bb12; PREPRO, fed a diet containing Synergy1, LGG and BB12. Ten days after beginning the diets, rats were treated with AOM (15 mg/kg s.c. two times); dietary treatments were continued for the entire experiment. Thirty-one weeks after AOM, rats treated with Synergy1 (PRE and PREPRO groups) had a significantly lower (P < 0.001) number of tumours (adenomas and cancers) than rats without Synergy1 (colorectal tumours/rat were 1.9 +/- 1.7, 1.1 +/- 1.1, 2.2 +/- 1.4 and 0.9 +/- 1.2 in Controls, PRE, PRO and PREPRO groups, respectively, means +/- SD). A slight, not significant effect of probiotics in reducing malignant tumours was also observed (P = 0.079). Caecal short-chain fatty acids (SCFA) were higher (P < 0.001) in the groups treated with Synergy1. Apoptosis was increased in the normal mucosa of the PRO group, while no variation was observed in the tumours. Colonic proliferation was lower in the PRE group as compared with Controls. Glutathione S-transferase placental enzyme pi type expression, and to a lesser extent, inducible NO synthase were depressed in the tumours from rats in the PRE and PREPRO groups. Cycloxygenase-2 expression was increased in the tumours of control rats but not in those from PRE, PRO or PREPRO rats. In conclusion, prebiotic administration in the diet decreases AOM-induced carcinogenesis in rats.
Femia
Angelo Pietro
AP
Department of Pharmacology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
Luceri
Cristina
C
Dolara
Piero
P
Giannini
Augusto
A
Biggeri
Annibale
A
Salvadori
Maddalena
M
Clune
Yvonne
Y
Collins
Kevin J
KJ
Paglierani
Milena
M
Caderni
Giovanna
G
D000230:Adenocarcinoma / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity; D001644:Bifidobacterium / Q000502:physiology*; D002273:Carcinogens / Q000633:toxicity; D002432:Cecum; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D004032:Diet; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005766:Gastrointestinal Contents; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007444:Inulin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007527:Isoenzymes / Q000378:metabolism; D007778:Lactobacillus / Q000502:physiology*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009844:Oligosaccharides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019936:Probiotics / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D005232:Fatty Acids, Volatile; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009844:Oligosaccharides; C120489:oligofructose; D007444:Inulin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496558:Gstp1 protein, rat; D001397:Azoxymethane