Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer

Abstract

Elevated tissue levels of prostaglandin E2, produced by cyclooxygenase (COX), are an early event in colorectal cancer (CRC). Data suggest the efficacy of nonsteroidal anti-inflammatory drugs, such as cancer preventives, in the inhibition of COX activity; however, side effects of nonsteroidal anti-inflammatory pose unacceptable limitations. Ginger has been reported to have anti-inflammatory activities with significant CRC preventive potential. We investigated whether consumption of 2.0 g ginger daily regulated the level of two key enzymes that control prostaglandin E2 production, COX-1 and NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Thirty participants at normal and 20 participants at increased risk for CRC were randomized and given 2.0 g/day ginger or placebo for 28 days. Flexible sigmoidoscopy was used to obtain colon biopsies at baseline and the end of the study. Tissue levels of COX-1 and 15-PGDH were assessed using western blotting. After ginger consumption, participants at increased risk for CRC had a significantly reduced colonic COX-1 protein level (23.8±41%) compared with the placebo group (18.9±52%; P=0.03). Protein levels of 15-PGDH in the colon were unchanged. In participants who were at normal risk for CRC, neither protein levels of COX-1 nor 15-PGDH in the colon were altered by ginger consumption. Ginger significantly lowered COX-1 protein expression in participants at increased risk for CRC but not in those at normal risk for CRC. Ginger did not alter 15-PGDH protein expression in either increased or normal-risk participants. Further investigation, in larger studies with a longer ginger intervention, is needed to examine the ability of ginger to impact tissue levels of prostaglandin.

Figures

Figure 1

COX-1 and 15-PGDH protein expressions in colon biopsies from healthy participants. Representative immunoblots of COX-1, 15-PGDH and actin protein level are shown (A). The quantification of the immunoblots is shown for COX-1 (top panel) and 15-PGDH (bottom panel). Values are expressed as ratio of post/pretreatment for COX-1or 15-PGDH protein/actin protein for each participant with normal risk of CRC. Results are expressed as mean ± SEM (n = 14 in ginger group and n = 16 in placebo group).

Figure 2

COX-1 and 15-PGDH protein expressions in colon biopsies from high CRC participants. Representative immunoblots of COX-1, 15-PGDH and actin protein level are shown (A). The quantification of the immunoblots is shown for COX-1 (top panel) and 15-PGDH (bottom panel). Values are expressed as ratio of post/pretreatment for COX-1or 15-PGDH protein/actin protein for each participant with high risk of CRC. Results are expressed as mean ± SEM (n = 10 in both placebo and ginger groups).