TA401

1,6,6-Trimethyl-2-((4-methylpiperazin-1-yl)methyl)phenanthrol[1,2-b]furan-7,10,11(6H)-trione (TA401), a newly synthesized tanshinone IIA analog, was developed to enhance the anti-tumor effect of CPT-11 in combined therapy and alleviate its gastrointestinal side effect. The combined cytotoxicity on HT29 and HCT116 colorectal cancer cells induced by TA401 and CPT-11 was comprehensively evaluated in vitro. The classical apoptosis pathway, including Bax, BCL-2, caspase 3, the phosphorylation level of ERK and AKT, was also examined to illustrate molecular mechanisms of the synergistic apoptosis both in vitro and in vivo. Synergistic suppression of colorectal cancer cell proliferation by TA401 and CPT-11 was observed at a fixed ratio (TA401:CPT-11 at 1:20). The apoptosis induced by combined treatment was triggered by activation of classical apoptotic pathway and decreased expression of TOP I, which was further confirmed in vivo. In addition, diarrheic side effect of CPT-11 was reduced by TA401 in the combined treatment. TA401 effectively promoted the anti-tumor effects of CPT-11 with alleviated side effects, which may be developed as a potential candidate for the combined therapy with CPT-11 against colorectal cancer.