Coffee, but Neither Decaffeinated Coffee nor Caffeine, Elicits Chemoprotection Against a Direct Carcinogen in the Colon of Wistar Rats

Nutr Cancer. 2019;71(4):615-623. doi: 10.1080/01635581.2018.1506489. Epub 2018 Oct 26.


Colorectal cancer (CRC) is the third most frequent malignancy worldwide. Coffee is the second most consumed drink in the globe and suggested to decrease the CRC risk. Here, we explored whether coffee, decaffeinated coffee, or caffeine impact on the development of colorectal carcinogenesis induced by the direct carcinogen N-methyl-N-nitro-N-nitrosoguanidine (MNNG) in rats. To this end, sixty-four young male Wistar rats were divided into eight groups of eight animals each. We analyzed the frequency of dysplastic crypts and expression of metallothionein as a biomarker of the cancer risk, as well the expression of phosphorylated H2A histone family/member X (γH2AX) for DNA damage and cyclooxygenase-2 (COX-2) for inflammatory response. We also studied the oxidative stress profile in hepatic and colonic frozen samples (malondialdehyde [MDA], glutathione [GSH], and α-tocopherol). We found that coffee but neither decaffeinated coffee nor caffeine decreased the development of dysplastic crypts in MNNG-exposed rats. All treatments reduced DNA damage intensity in colonocytes. Only decaffeinated coffee increased the numbers of metallothionein positive crypts in comparison with coffee-treated rats. Coffee and caffeine inhibited COX-2 expression in the colon. Both decaffeinated coffee and caffeine decreased hepatic α-tocopherol levels. We suggest that coffee may have other compounds that elicit greater chemoprotective effects than caffeine reducing the CRC risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Caffeine / pharmacology*
  • Carcinogens / toxicity*
  • Coffee* / chemistry
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / prevention & control*
  • Cyclooxygenase 2 / metabolism
  • DNA Damage / drug effects
  • Histones / metabolism
  • Male
  • Metallothionein / metabolism
  • Methylnitronitrosoguanidine / toxicity
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • alpha-Tocopherol / metabolism


  • Anticarcinogenic Agents
  • Carcinogens
  • Coffee
  • Histones
  • Methylnitronitrosoguanidine
  • Caffeine
  • Metallothionein
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • alpha-Tocopherol