Curcumin for chemoprevention of colon cancer

Abstract 

The most practical approach to reduce the morbidity and mortality of cancer is to delay the process of carcinogenesis through the use of chemopreventive agents. This necessitates that safer compounds, especially those derived from natural sources must be critically examined for chemoprevention. A spice common to India and the surrounding regions, is turmeric, derived from the rhizome of Curcuma longa. Pre-clinical studies in a variety of cancer cell lines including breast, cervical, colon, gastric, hepatic, leukemia, oral epithelial, ovarian, pancreatic, and prostate have consistently shown that curcumin possesses anti-cancer activity in vitro and in pre-clinical animal models. The robust activity of curcumin in colorectal cancer has led to five phase I clinical trials being completed showing the safety and tolerability of curcumin in colorectal cancer patients. To date clinical trials have not identified a maximum tolerated dose of curcumin in humans with clinical trials using doses up to 8000mg per day. The success of these trials has led to the development of phase II trials that are currently enrolling patients. Overwhelming in vitro evidence and completed clinical trials suggests that curcumin may prove to be useful for the chemoprevention of colon cancer in humans. This review will focus on describing the pre-clinical and clinical evidence of curcumin as a chemopreventive compound in colorectal cancer.

Abbreviations: 5-FU, 5-fluoruouracil, ATF-2, activating transcription factor 2, AP-1, activator protein-1, AIF, apoptosis inducing factor, AHR, aryl hydrocarbon receptor, Arnt, aryl hydrocarbon receptor nuclear translocator, AUC, area under the curve, JNK, c-jun N-terminal kinase, CYP1, cytochrome P450-1 family, EGFR, epidermal growth factor, FAP, familial adenomatous polposis, GADD153, growth arrest and DNA damage, HNPCC, hereditary nonpolyposis colorectal cancer, IκB, IkappaB, IL-1, interleukin-1, LPS, lipopolysaccharide, MTHFR, methylenetetrahydrolfolate reductase, MAPK, mitogen activated kinase, NAT1 and NAT2, N-acetyltransfereases, NSAIDs, non-steroidal anti-inflammatory drugs, NF-κB, nuclear factor-kappa B, PPAR-γ, peroxisome proliferator activator receptor-gamma, PKC, protein kinase C, Smac, second mitochondria derived activator of caspase, SCC, squamous cell carcinoma, SULT1A1 and SULT1A3, sulfotransferase, TNF-α, tumor necrosis factor-alpha, UGTs, UDP-glucuronosyltrasferases

Keywords: Curcumin, Turmeric, Colon, Cancer, Chemoprevention, COX-2