Table 4.
Studies using the AOM model to evaluate several therapeutic strategies for colorectal cancer.
| Animal Strain and Gender | Carcinogenic Administration Route | Drugs or Compounds Evaluated (Classification) | Dose/Treatment | Therapeutic Effects (Ref) |
|---|---|---|---|---|
| F344 male rats | s.c. injections 15 mg/kg b.w./wk once a week for 2 wks | Ursodeoxycholic acid and cholic acid (bile acids) | p.o.(0.2% or 0.4% cholic acid, 0.2% or 0.4% ursodeoxycholic acid, 0.2% cholic acid + 0.2% ursodeoxycholic acid) for 30 wks | Higher dose of ursodeoxycholic acid reduced the incidence of colorectal tumors [58] |
| s.c. 15 mg/kg bw once weekly for 2 wks | Celecoxib (a non-steroidal anti-inflammatory drug) | p.o. (500, 1000 or 1500 ppm) before exposure to AOM, during treatment, and until termination of the study at 52 wks | Chemopreventive activity in all tumor stages [59] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | iNOS inhibitor L-N6 -(1-iminoethyl) lysine tetrazole-amide (SC-51), celocoxib (nonsteroidal anti-inflammatory) | p.o. (10, 30 or 100 ppm SC-51; 500 ppm celocoxib; 30 or 100 ppm SC-51 + 500 ppm celocoxib) for 8 wks | The combination of SC-51 with celocoxib was more effective in colorectal cancer prevention than the compounds alone [60] | |
| s.c. 15 mg/kg b.w. 1x/wk for 3 wks | Rebaudioside A, oleanolic acid, costunolide and soyasionin A2 (terpenoids), liquiritin (flavonoid), phyllodulcin and hydrangenol (isocumarins) | p.o. (200 ppm of each) for 5 wks | Costunolide is the most effective chemopreventive agent [61] | |
| s.c. 29.6 mg/kg b.w. | Piroxicam (a non-steroidal anti-inflammatory drug) and D, L-α-difluoromethylornithine (DFMO) | p.o. (25, 75 and 150 ppm piroxicam or 400, 1000 and 4000 ppm DFMO) 1 wk after AOM for 26 wks | A combination of piroxicam and DFMO was more effective in the inhibition of colorectal cancer than compounds alone [62] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | Phenylethyl-3-methylcaffeate (PEMC) | p.o. (750 ppm) 2 wks before AOM for 52 wks | Inhibited colonic tumors [63] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks; start 2 wks after diet | Celocoxib (COX-2 inhibitor) | p.o. (1500 ppm) for 50 wks | Chemopreventive activity [64] | |
| s.c. 15 mg/kg b.w. at 7 and 8 wks of rat age | S-methylmethane thiosulfonate (S-MMTS) (isolate from cauliflower) and sulindac | p.o. (80 ppm S-MMTS, 160 ppm sulindac or 40 ppm S-MMTS + 160 ppm sulindac) 14 wks after AOM for | A combination of S-MMTS and sulindac was more effective in the inhibition of colorectal cancer than compounds alone [65] | |
| s.c. 15 mg/kg 1x/wk for 2 wks | Naproxen and NO-naproxen (nonspecific nonsteroidal anti-inflammatory drugs) | p.o. (200 or 400 ppm naproxen and 300 or 600 ppm nitric oxide-naproxen) 3 days after AOM for 8 wks | Chemopreventive effects [66] | |
| 15 mg/kg i.p. 1x/wk for 2 wks | Lovastatin (statin) and exisulind (selective apoptotic antineoplastic drug) | p.o. (50 ppm lovastatin, 100, 250 or 1000 ppm exisulind alone or in combination with 50 ppm lovastatin) for for 4 wks | Chemopreventive effects of lovastatin but not exisulind [67] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | CP-31398 (p53-modulating agent) and celocoxib (non-steroidal anti-inflammatory drug) | Diet supplemented (1, 150 or 300 ppm CP-31398, 300 ppm celecoxib or 1500 ppm CP-31398 + 300 ppm celecoxib) 2 wks after AOM and for 48 wks | A combination of compounds enhanced colorectal cancer chemopreventive efficacy [68] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | Aspirin (a non-steroidal anti-inflammatory drug) | p.o. (0, 200 or 400 ppm) daily 2 wks before AOM and for 52 wks | Inhibited incidence and multiplicity of colorectal carcinomas [69] | |
| s.c. injection 15 mg/kg b.w. 1x/wk for 2 wks | Prebiotic germinated barley foodstuff (a mixture of insoluble protein and dietary fiber) | Diet supplemented with prebiotic germinated barley foodstuff for 4 wks | Anti-tumorigenicity activity [70] | |
| i.p. 15 mg/kg b.w. | Aspirin (a non-steroidal anti-inflammatory drug) and α-Difluoromethylornithine (DFMO) (ornithine decarboxylase inhibitor) | p.o. (Exp1.: 0, 200, 600 or 1800 mg/kg/diet of aspirin or 1000 mg/kg diet of DFMO; 8 days before 1st AOM; Exp.2: 200, 600, 1800 mg/kg/diet aspirin or 1000 or 3000 mg/kg/diet of DFMO or 1000 mg/kg/diet DFMO + 200 or 600 mg/kg/diet aspirin; 8 days before 1st) for 43 wks after last AOM | The combination of aspirin and DFMO after AOM reduced colorectal tumors [71] | |
| s.c. 15 mg/kg b.w 1x/wk for 2 wks | Vitamin D, acetylsalicylic acid (a non-steroid anti-inflammatory drug) and calcium | Diet supplemented (0, 2500, 5000 or 7500 ppm calcium; 0 or 300 ppm acetylsalicylic acid alone or combination with 0 or 0.02 µg/kg diet vitamin D) 20 days before AOM and for 18 wks | Increased incidence of tumors with high levels of calcium alone or in combination with vitamin D; Vitamin D with acetylsalicylic acid also increased tumor incidence [72] | |
| s.c. 8 mg/kg b.w./wk for 10 wks | Dietary wheat bran and dehydrated citrus fiber (in form of orange peel) | Diet supplemented (0 or 15% wheat bran or citrus fiber) for 20 wks | Reduced the risk of colorectal tumors [24] | |
| s.c. 15 mg/kg 1x/wk for 2 wks) | Tea extracts, Polyphenols and epigallocatechin gallate (EGCG) | d.w. (360 or 3600 ppm black and green tea extracts; 360 or 1800 ppm EGCG; 360 or 1800 black tea polyphenols and 360 or 3600 green tea polyphenols) at 6 wks and for 43 wks | No effect in tumor incidence [73] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks) | Aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and atorvastatin (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) |
Diet supplemented (150 ppm atorvastatin, 600 pp celecoxib, 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib or 100 ppm atorvastatin + 200 ppm aspirin) one day after AOM and for 42 wks | Inhibited the incidence and multiplicity of colorectal carcinomas alone or in combination [74] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | Grape seed extract (GSE) | Diet supplemented (0.25 or 0.5% (w/w) GSE) 1 wk before AOM, 4 wks last AOM or during all study and for 16 wks | Chemopreventive efficacy against early steps of colorectal carcinogenesis [75] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks) | Celecoxib (cyclooxygenase-2 inhibitor) in diets high in mixed lipids (HFML) or fish oil (HFFO) | Diet supplemented (0, 250, 500, or 1000 ppm celecoxib with HFML or HFFO diet) one day after AOM and for 26 wks | Preventive effect of low doses of celecoxib in HFFO diet [76] | |
| F344 female rats | i.p. 20 mg/kg b.w. | Polyethylene-glycol (PEG) (non-fermented polymer) | Diet supplemented (3 g/kg b.w/day) 7 days after AOM and for 105 days | Chemopreventive effects [77] |
| i.p. 20 mg/kg b.w. | Heme in food (in form of chicken, beef, black pudding) | Diet supplemented (600 g/kg diet chicken, beef and black pudding) 7 days after AOM and for 100 days | Increased colorectal carcinogenesis for all compounds [78] | |
| s.c. 8 mg/kg b.w./wk for 10 wks | Alfalfa, pectin and wheat bran | Diet supplemented (0 or 15% alfalfa, pectin and wheat bran) for 40 wks after 1st AOM | Inhibited colorectal tumor incidence, especially by pectin or wheat bran [79] | |
| BALB-c female mice | i.p. 15 mg/kg1x/wk for 2 wks | Kefir (a probiotic fermented milk product) | p.o. (5 mL/kg b.w. fermented kefir milk) for 8 wks | Decreased and prevented the growth of colorectal tumors [80] |
| Sprague-Dawley male rats | s.c. 15 mg/kg 1x/wk for 2 wks, 28 days after diet supplementation | Amylose maize starch and butyrylated high-amylose maize starch | Diet supplemented (10% of high-amylose maize starch or 10% butyrylated alone or in combination) start at day 0 until euthanasia | The compound combination reduced the risk of developing colorectal cancer [81] |
| i.p. 15 mg/kg 1x/wk for 4 wks | indomethacin and copper-indomethacin (non-steroidal anti-inflammatory drug) | i.p. (3.0 mg/kg indomethacin or 3.8 mg/kg copper-indomethacin) daily | Both compounds showed chemopreventive activity, but indomethacin was more effective [82] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | R-Flurbiprofen (non-steroidal anti-inflammatory drug) | Gavage (30 mg/kg b.w./per day) 6 days a week, 1 wk before AOM and for 30 wks | Protective effects against colorectal cancer development [83] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks, at day 45 of rat’s life | Soy isoflavones | p.o. (0, 40 100 mg/kg diet) from birth, including pregnancy and lactation, until 26 wks of life. AOM at day 45 | Lifetime exposure suppressed colon tumors growth [84] | |
| s.c. 15 mg/kg b.w. 1x/wk for 2 wks | Probiotic bacteria “bifidobacterium lactis” (B. lactis) and carbohydrate “resistant starch” (from a commercial source called Hi-maize 958 or Hi-maize S260) | Diet supplemented (100 g/kg/diet of Hi-maize 958 or Hi-miaze 260 and 1% lyophilized culture of B. lactis) | Protective effects by the combination of the two products [85] | |
| s.c. 15 mg/kg b.w. for three weekly doses | Xanthohumol (a polyphenol isolated from Humulus lupulus L.) | Gavage (5 mg/kg b.w.) every alternate day for 8 wks | Inhibited cell proliferation and induced apoptosis [86] | |
| Wistar rats | i.p. 15 mg/kg | L-lysine, propolis, or gum arabic | Gavage water (150 mg/kg L.-lysine, 100 mg/5 mL/kg propolis or 5 mL/kg gum arabic) daily for 16 wks | Gum arabic and propolis reduced the total number of aberrant crypt foci, L-lysine neither protected against nor enhanced colorectal cancer [87] |
b.w.: body weight; d.w.: drinking water; i.p.: intraperitoneal injection; p.o.: per os; s.c.: subcutaneous injection; wk: week; wks: weeks.