Abstract
Colorectal cancer (CRC) is the third most common type of cancer and the fourth most common cause of cancer-related death worldwide. The incidence and mortality of CRC are higher in more developed regions than in less developed regions and they are also higher in males than in females from 45.7% to 7% and from 16.1% to 5.5%, respectively. These and other data suggest CRC may be amenable to improve prevention by suitable lifestyle interventions, including dietary modification. Quercetin (QC) is a flavonoid obtained from plants that can reach concentrations in the gastrointestinal tract in the range of 0.16–1.30 µM as determined by LC-MS analysis of faecal water. However, many other compounds are also present in faecal water, including those from other plants (e.g. SFN released from brassicas) and DHCA (3,4-dihydroxyphenylpropionic acid), which is a colonic microflora catabolite of the major dietary phenolic acids, derived from the consumption of fruits, vegetables, coffee, and tea. The investigation was done to assess the cytotoxic effect of individual components in human colon adenocarcinoma (Caco-2) cells and primary human colonic epithelial cells (HCoEpiC). It also investigates whether synergistic interactions or additive interactions occur between mixtures of QC, DHCA, and SFN in terms of potential cytotoxic activity in Caco-2 and HCoEpiC and it compares the effects observed in the cancer cell line with those in HCoEpiC. The study demonstrated that Caco-2 cells or HCoEpiC were treated with various concentrations of QC (0-150 µM), DHCA (0-500 µM) or SFN (0-200 µM) individually and in combination, to determine the half maximal inhibitory concentration (IC50) value using the methylthiazol tetrazolium (MTT) assay. This has resulted in that QC and SFN had both concentration and time-dependent cytotoxic effects on Caco-2 cells (IC50 50 µM, p > 0.001 and 32 µM, p > 0.0001 for QC and 45 µM, p > 0.05 and 20 µM, p > 0.0001 for SFN after 24 and 48 h, respectively). DHCA only showed detectable cytotoxic effect in Caco-2 cells at the highest concentration tested. QC had no detectable cytotoxic effect on HCoEpiC, while SFN showed a very similar cytotoxic effect in HCoEpiC (IC50 19.21 µM, p > 0.0001), DHCA had no cytotoxic effect. However, SFN supplementation increased QC cytotoxicity in Caco-2 and HCoEpiC at low concentrations. Moreover, DHCA appeared to cause an increase in viability or cell number at all SFN concentrations tested in HCoEpiC but not in HCoEpiC. DHCA supplementation had a clear influence on QC-induced cytotoxicity in Caco-2 and but not in HCoEpiC. In conclusion, combinations of the phytochemicals at low concentrations exhibited even greater cytotoxic effects than phytochemicals individually in CRC cells and they do not have an effect on primary. These data suggest the three phytochemicals each exhibit unique and distinct effects in CRC and primary colon cells. It is clear from the present studies that some combinations of phytochemicals can have an additive interaction effect rather than a synergistic interaction in CRC growth cells. In summary, evidence suggests that a combination of phytochemicals is a good candidate for further anticancer studies.