COX-2 inhibitors, a form of non-steroidal antiinflammatory drug (NSAID) that targets the COX-2 enzyme,  have been recognized for their ability to prevent the growth of colon tumors. They have, however, also been proven to seriously increase the risk for heart attacks and strokes. The authors of paper published recently in the journal Current Colorectal Cancer Reports despite the early hopes for these medications:

“”Nonsteroidal anti-inflammatory drugs are one of the more studied groups of drugs in colorectal cancer chemoprevention because both epidemiological and experimental studies have shown that these drugs reduce the risk of developing colonic tumors. Cyclooxygenase-2 (COX-2), an isoform of cyclooxygenase, plays an important role in colorectal carcinogenesis…However, recent long-term studies have shown that these agents and probably some NSAIDs have an increased risk of cardiovascular events, which has changed the whole scenario.”

In another paper published in the subsequent issue of the same journal, the authors state:

“Recent studies of coxibs indicate that these agents are effective in reducing sporadic adenoma recurrence, but chronic use can result in serious cardiovascular toxicity. These data underscore the need for chemopreventive agents with acceptable risk-to-benefit ratios.”

Happily, a study published in the Annals of the New York Academy of Sciences offers evidence that curcumin, the benign natural phenol extracted from the spice turmeric, also offers a way to inhibit the COX-2 enzyme for colorectal cancer chemoprevention.

“…the AMPK cascade has emerged as an important pathway implicated in cancer control. In this study we investigated the effects of curcumin on apoptosis and the regulatory effect of the AMPK–cyclooxygenase-2 (COX-2) pathway in curcumin-induced apoptosis. Curcumin has shown promise as a chemopreventive agent because of its in vivo regression of various animal-model colon cancers. This study focused on exploiting curcumin to apply antitumorigenic effects through modulation of the AMPK–COX-2 cascade.”

Did curcumin show enough activity in this regard to be meaningful?

“Curcumin exhibited a potent apoptotic effect on HT-29 colon cancer cells at concentrations of 50 μmol/L and above. These apoptotic effects were correlated with the decrease in pAkt and COX-2, as well as the increase in p-AMPK.”

They further demonstrated that blocking the effect of curcumin resulted in an increase in COX-2 expression resulting in a replacement of apoptosis (cancer cell death)with proliferation. The authors add in conclusion:

“These results indicate that AMPK is crucial in apoptosis induced by curcumin and further that the pAkt–AMPK–COX-2 cascade or AMPK–pAkt–COX-2 pathway is important in cell proliferation and apoptosis in colon cancer cells.”

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This recent study published in the journal Lipids reveals compelling evidence that tocotrienols are much more effective at reducing inflammation by inhibiting cyclooxygenase-2 gene expression (COX-2) than the common alpha-tocopherol form of vitamin E. The authors state: “Tocotrienols are powerful chain breaking antioxidants. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions.” They note that different tocotrienols vary in which pro-inflammatory signalling path they inhibit, and go on to conclude: “Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than α-tocopherol and the most effective form is δ-tocotrienol,” although careful reading suggests that a mixed tocotrienol supplement would be most desirable as a safe and side-effect free natural anti-inflammatory agent.

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