Farrerol Ester Inhibits Colorectal Carcinoma Cell Growth via Downregulation of STAT3 Pathway

The present study investigated the effect of farrerol ester on colorectal carcinoma cell growth and explored the underlying mechanism. The results demonstrated that incubation with 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mu M concentrations of farrerol ester caused a significant (p < 0.05) reduction in DLD1 and SW480 CRC cell viability in dose-dependent manner. Incubation with 0.5, and 3.0 mu M concentrations of farrerol ester led to a significant (p < 0.05) decrease in CRC cell colony formation. Farrerol ester treatment at 0.5, and 3.0 mu M concentrations led to a significant reduction in DLD1 and SW480 cell invasion potential after 72 h. Moreover, decrease in cell invasion was higher in 3.0 mu M farrerol ester-treated cells compared to the 0.5 mu M-treated cells. The expression of p-p85 and p-Akt proteins was markedly reduced in DLD1 and SW480 CRC cells on treatment with farrerol ester at 0.5, and 3.0 mu M concentrations. Decrease in p-p85 and p-Akt protein expression by farrerol ester was maximum in DLD1 and SW480 cells treated with 3.0 mu M concentration compared to the 0.5 mu M treated cells. Farrerol ester treatment caused a remarkable reduction in the expression of nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription 3 (STAT3) in DLD1 and SW480 cells. In summary, farrerol ester inhibits DLD1 and SW480 CRC cell proliferation, suppresses colony forming potential and decreases invasiveness. Treatment of DLD1 and SW480 CRC cells with farrerol ester also alleviated the expression of p-p85 and p-Akt proteins. The expression of nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription 3 (STAT3) was also targeted in CRC cells by farrerol ester treatment. Thus, farrerol ester targets PI3K/Akt/mTOR pathways in colorectal carcinoma cells and therefore can be developed as an effective therapeutic agent for colorectal carcinoma treatment.