Health Benefits of Coffee Consumption for Cancer and Other Diseases and Mechanisms of Action

Abstract

Coffee is one of the most widely consumed beverages worldwide, and epidemiology studies associate higher coffee consumption with decreased rates of mortality and decreased rates of neurological and metabolic diseases, including Parkinson's disease and type 2 diabetes. In addition, there is also evidence that higher coffee consumption is associated with lower rates of colon and rectal cancer, as well as breast, endometrial, and other cancers, although for some of these cancers, the results are conflicting. These studies reflect the chemopreventive effects of coffee; there is also evidence that coffee consumption may be therapeutic for some forms of breast and colon cancer, and this needs to be further investigated. The mechanisms associated with the chemopreventive or chemotherapeutic effects of over 1000 individual compounds in roasted coffee are complex and may vary with different diseases. Some of these mechanisms may be related to nuclear factor erythroid 2 (Nrf2)-regulated pathways that target oxidative stress or pathways that induce reactive oxygen species to kill diseased cells (primarily therapeutic). There is evidence for the involvement of receptors which include the aryl hydrocarbon receptor (AhR) and orphan nuclear receptor 4A1 (NR4A1), as well as contributions from epigenetic pathways and the gut microbiome. Further elucidation of the mechanisms will facilitate the potential future clinical applications of coffee extracts for treating cancer and other inflammatory diseases.

Keywords: AH receptor; Nrf2; coffee; health; redox.

Figure 1

Structures of individual compounds in roasted coffee after extraction with hot water.

Figure 2

Development of intracellular oxidative stress is attenuated by coffee-induced stress. Coffee-induced stress results in the dissociation of NRF2 from KEAP and the subsequent translocation of NRF2 into the nucleus where the NRF2-sMAF complex binds cis-acting AREs to induce NRF2 regulated genes/pathways, including the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), quinone oxidoreductase 1 (NQO1), glutathione reductase (GR), harm oxygenase 1 (HO-1), and several thioreductases family members [104,105,106,107].

Figure 3

Coffee extracts induce ROS. Treatment of cancer cells with ROS inducers, such as chlorogenic acids and quercetin, inhibits redox enzymes and decreases mitochondrial membrane potential (MMP) to induce ROS, which downregulates cMyc + cMyc-regulated microRNAs (miRs: miR 17-92/27a). This results in the induction of ZBTB genes (ZBTB4, ZBTB10) + inhibition of pro-oncogenic Sp1/Sp3/Sp4-regulated genes/pathways [127,128,129,130,131,132,133].

Figure 4

Coffee receptor-mediated responses: coffee extracts that bind AhR (A) or NR4A1 (B) may activate age- and cell-context-dependent chemopreventive and/or chemotherapeutic responses [156,157,158,159,160,161].