Therapeutic efficacy of baicalein and 6-(methylsulfinyl)hexyl isothiocyanate, alone or in combination with 5-fluorouracil, in the treatment of colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy worldwide. 5-fluorouracil (5-FU) remains the first-line drug for treatment of the metastatic stage despite the limits of its efficacy. Here, we investigated the anti-tumor effect of two phytochemicals, baicalein and 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC), on colorectal cancer cells (HCT-116 and RKO) and determined whether these individual agents, when used alone or in combination with 5-FU, could enhance treatment efficacy. The evaluations included assays that measure cell viability and proliferation (MTT), apoptosis, cell migration, cell cycle, gelatin zymography, and combination index analyses. In both cell lines, baicalein [HCT-116 cells; IC50 = 40.82 ± 7.77 μM (24 h) and 33.83 ± 1.99 μM (48 h), and RKO cells; IC50 = 55.84 ± 3.12 μM (24 h) and 45.11 ± 3.05 μM (48 h)] and 6-MITC [HCT-116 cells; IC50 = 24.66 ± 1.57 μM (24 h) and 8.28 ± 0.56 μM (48 h), and RKO cells; IC50 = 45.74 ± 1.63 μM (24 h) and 9.85 ± 1.42 (48 h) μM] suppressed cancer cell proliferation in a dose-dependent manner at 24 and 48 h, while 5-FU was cytotoxic only after 48 h [HCT-116 cells; IC50 18.43 ± 3.82, and RKO cells; IC50 = 30.57 ± 8.34 μM]. Compared with 5-FU treatment only, the combined treatments induced significant increases in the pre-G1 phase and decreases in the G1 and S phases in both cell lines. In HCT-116 cells, combined treatments induced significantly greater apoptosis compared to 5-FU alone. Single and combination treatments with baicalein or 6-MITC significantly lowered the migration of cells compared to 5-FU alone in both cell lines. In conclusion, our study showed that both baicalein and 6-MITC induced similar anti-tumor effects compared to 5-FU alone in both cell lines, however, the combined treatments were more efficient.