Curcumin potentiates the pro-apoptotic effects of sulindac sulfone in colorectal cancer.
OBJECTIVE
The use of sulindac sulfone (SFN) for colorectal cancer (CRC) therapy is limited due to its toxicity. The present study was carried out to examine whether curcumin, a novel chemopreventive agent, can potentiate the effects of low dosages of SFN in CRC treatment.


METHODS
HT-29 CRC cells were exposed to SFN (200 - 400 microM), curcumin (5 - 10 microM) or their combination. The cytotoxic effects of the drugs were evaluated using growth inhibition assays. Annexin V/PI and cell cycle analysis were employed to study the mechanism of action of the drugs. The therapeutic efficacy of the drugs in vivo was examined using the aberrant crypt foci (ACF) model. The treatment groups included eight rats/group.


RESULTS
Treatment of cells with curcumin and SFN resulted in a synergistic inhibitory effect of 50 - 90% (p < 0.005) on cell growth. Growth inhibition was associated with inhibition of proliferation, G2/M arrest and induction of apoptosis. Administration of curcumin (0.6%) and SFN (0.06%) to 1, 2-dimethylhydrazine treated rats significantly reduced (by 75%, p < 0.01) the number of ACF.


CONCLUSIONS
Curcumin augments the therapeutic effects of SFN. This may be clinically important since the addition of curcumin to low dosages of SFN may encourage a safer and potent combinatorial treatment regimen for CRC.
Giladi
Nis
N
Sapir Medical Center, Department of Surgery B, Kfar Saba, Tel Aviv, Israel.
Kazanov
Diana
D
Shpitz
Baruch
B
Aroch
Ilan
I
Kraus
Sarah
S
Arber
Nadir
N
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003474:Curcumin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019073:HT29 Cells; D006801:Humans; D008297:Male; D011230:Precancerous Conditions / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives
D013467:Sulindac; D003474:Curcumin; C025463:sulindac sulfone