Potential chemoprotective effects of the coffee components kahweol and cafestol palmitates via modification of hepatic N‐acetyltransferase and glutathione S‐transferase activities

Abstract

Coffee drinking has been associated with reduced incidence of colorectal cancer, possibly via chemoprotection/modification of the metabolism of dietary heterocyclic amine carcinogens such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) by kahweol and cafestol palmitates (K/C), two components of unfiltered coffee. Using the PhIP-exposed male Fisher F344 rat as a model, K/C have been shown to reduce colonic PhIP-DNA adducts by > 50%. We have used the male F344 rat to investigate the effects of dietary K/C (0.02-0.2% as a 1:1 mixture) on the metabolism of PhIP by N-acetyltransferase- (NAT), sulfotransferase- (SULT), and glutathione-dependent pathways. K/C decreased hepatic NAT-dependent PhIP activation by up to 80% in a dose-dependent manner. Conversely, hepatic glutathione S-transferase (GST) activity/expression increased, e.g., 3-4 fold toward 1-chloro-2,4-dinitrobenzene (total activity), up to 23-fold toward 4-vinylpyridine (rGSTP1), and approximately 7-fold for rGSTA2 protein. These effects had fully developed after 5 days of the test diet and persisted for at least 5 days after withdrawal of K/C. Hepatic glutathione increased two- to threefold and this increase was more short-lived than other changes. K/C did not modify hepatic SULT activity or colon NAT and GST activities. Benzylisothiocyanate and black tea, which have also been shown to reduce the formation of PhIP-DNA adducts in this model, had little effect on hepatic NAT, SULT, GST, or GSH. In primary culture of rat hepatocytes, both kahweol and cafestol palmitates reduced NAT activity by 80%. In summary, the unique potential of K/C to convert rapid acetylators to a slow acetylator phenotype, accompanied by GST induction, might contribute to chemoprevention against cancers associated with heterocyclic amines.

Coffee consumption and human health - beneficial or detrimental? - Mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus

“…Recently, coffee diterpenes were found to increase the GSH and c-GCS level in a hepatoma cell line in a dose-dependent manner [79] and hepatic GSH and GSH S-transferase (GST) activity in rats [80]. These data suggested that coffee diterpenes have chemoprotective effects through stimulation of the endogenous antioxidant system via a mechanism which presumably involves transcription factors, such as AP-1, Nrf2, and c-jun [81,82].…”

Coffee and gastric cancer: systematic review and meta-analysis

“…However, it can also inhibit carcinogenesis in vivo and alter carcinogen metabolism, decreasing the cytotoxic, cytostatic, or mutagenic activity of aromatic DNA-damaging compounds through a decrease in the concentration of free aromatic procarcinogens available for cytochrome activation 4,5 . The protective effects of coffee were partially ascribed to the potential for kahweol and cafestol palmitates to convert rapid acetylators into a slow acetylator phenotype 6 . These diterpenes may also have anti-inflammatory and anti-carcinogenic properties by interfering with nitric oxide 7 , prostaglandin E2 production, and cyclooxigenase-2 expression 8 .…”

Coffee and tea consumption, genotype-basedCYP1A2andNAT2activity and colorectal cancer risk-Results from the EPIC cohort study

“…It is hypothesized that the possibly protective effect of coffee against CRC found in some studies may be related to antioxidant and antimutagenic effects of phenolic compounds (mainly chlorogenic acid), 6,33 inhibition of colon cancer cell growth by caffeine, 8,9 and cafestol and kahweol mediated reduction of bile acid synthesis 2,34,35 and inhibition of CYP1A2 and NAT2 activity. [36][37][38][39] In addition, caffeine may specifically protect against distal colon cancer by increasing the motility of the distal colon and, as a consequence, lowering carcinogen exposure of colonic epithelial cells. 7 Although in the present study specific data on caffeinated and decaffeinated coffee was only available in approximately half of the participating centers, separate analyses for caffeinated coffee did not demonstrate a significant protective effect of caffeinated coffee against CRC.…”