Celecoxib and curcumin additively inhibit the growth of colorectal cancer in a rat model.
BACKGROUND
Multiple studies have indicated that specific COX-2 inhibitors may prevent CRC. However, the long-term use of COX-2 inhibitors is not toxicity-free and may be limited due to its cardiovascular side effects. The present study was carried out to examine the chemopreventive effects of celecoxib and curcumin alone and in combination using the 1,2-dimethylhydrazine (DMH) rat model.


METHODS
Male rats were injected with DMH and randomly divided into four groups that consumed one of the following diets: (a) AIN-076 control diet; (b) AIN-076/curcumin (0.6%); (c) AIN-076/celecoxib (0.16%), or (d) AIN-076/celecoxib (0.16%) and curcumin (0.6%). Aberrant crypt foci (ACF) were identified by intensive staining with methylene blue in comparison to the surrounding normal crypts.


RESULTS
The average number of ACF per rat colon was 64.2 +/- 3 in the control group, 39 +/- 5 and 47 +/- 10 for the curcumin- and celecoxib-treated group, respectively, and 24.5 +/- 6 in the group that had received both agents.


CONCLUSIONS
In vivo, curcumin augments the growth inhibitory effect of celecoxib. This may be clinically important as this dose of celecoxib can be achieved in human serum following standard anti-inflammatory dosing of 100 mg.
Shpitz
Baruch
B
Department of Surgery B, Sapir Medical Center, Kfar Saba, Israel.
Giladi
Nis
N
Sagiv
Eyal
E
Lev-Ari
Shahar
S
Liberman
Eliezer
E
Kazanov
Diana
D
Arber
Nadir
N
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001707:Biopsy, Needle; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007150:Immunohistochemistry; D008297:Male; D011336:Probability; D011720:Pyrazoles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D003474:Curcumin; D000068579:Celecoxib