Caffeic Acid Intervention Slows Cancer Cell Growth While Reversing the Th2-Biased Immune Balance in Human Colorectal...

The effects of caffeic acid (CA) intervention on the relationship between human colorectal cancer (CRC) HT-29 cell growth and Th1/Th2 immune balance in vivo are not fully understood. To unravel the perplexity, this study examined the impact of CA intervention on the relationship between tumor growth and the Th1/Th2 immune balance in CRC-bearing mice for 35 days using an established xenograft animal model. The BALB/c nude mice were subcutaneously xenografted with HT-29 cells and received three different CA doses daily, including 6 mg (low-dose), 30 mg (medium-dose), and 60 mg CA/kg AIN-93 M feed (high-dose). The results showed that CA intervention slightly decreased tumor volumes and weights in CRC-bearing mice. Meanwhile, the CRC-bearing mice tended to have a Th2-biased immune balance, as indicated by the cytokine secretion profile of splenocytes. Notably, CA intervention dose-dependently increased Concanavalin A-stimulated IFN-γ secretion and the IFN-γ (Th1)/IL-10 (Th2) secretion ratio. There is a negative correlation between IFN-γ/IL-10 secretion ratios and tumor weights, suggesting that higher doses of CA intervention may reverse the immune balance toward a Th1-dominant immune response in CRC-bearing mice. CA showed modest trends toward reduced tumor burden under the experimental conditions tested, while reversing the Th2-biased immune balance in CRC-bearing mice.