Comparison of the anti-proliferation and apoptosis-induction activities of sulindac, celecoxib, curcumin, and nifedipine in mismatch repair-deficient cell lines.
OBJECTIVE
The adenomatous polyposis coli (APC) and mismatch repair (MMR) pathways are both involved in the tumorigenesis of hereditary colorectal cancers. Chemoprevention focuses on the APC pathway in the absence of information concerning MMR targets. This study compared the anticancer effects of sulindac, celecoxib, curcumin, and nifedipine in MMR-deficient cell lines, in order to determine the most appropriate chemopreventive agent for long-term use in patients with hereditary colorectal cancer.


METHODS
Five human colorectal cell lines (SW480, HCT116, LoVo, SW48, and HCT15) and an endometrial cancer cell line (HEC-1-A) were used for susceptibility testing. Tests included assays for growth inhibition, cell-cycle arrest, and apoptosis.


RESULTS
Sulindac, celecoxib, curcumin, and nifedipine all displayed dose- and time-dependent anti-proliferation activities. Celecoxib was the most effective anti-proliferative agent, and increased the G0/G1 phase proportion in the cell cycle after treatment more significantly than the other agents in all cell lines. Curcumin displayed a more potent apoptosis-inducing activity than the other agents in treated cells.


CONCLUSIONS
The tested drugs were effective against colorectal and endometrial cancer cell lines. Celecoxib is more potent with fewer side effects than sulindac. Nifedipine's observed chemopreventive efficacy may complement its known therapeutic application in patients with hypertension.
Wei
Shu-Chen
SC
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Young-Sun
YS
Tsao
Po-Nien
PN
Wu-Tsai
Jyy-Ji
JJ
Wu
C H Herbert
CH
Wong
Jau-Min
JM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D018890:Chemoprevention / Q000379:methods; D015179:Colorectal Neoplasms / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013467:Sulindac / Q000494:pharmacology
D000970:Antineoplastic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D013467:Sulindac; D009543:Nifedipine; D003474:Curcumin; D000068579:Celecoxib