RESUMEN
Objective:To study the anti-colon cancer effect and mechanism of magnolol analogue CT2-3， in order to lay a foundation for the application of CT2-3 in anti-colon cancer area. Method:Colon cancer cells SW480 and LoVo were cultured in vitro. Different concentrations （10， 20， 40， 80 μmol·L-1） of CT2-3 and magnolol were used to stimulate colon cancer cells for 24， 48 h. The effect of CT2-3 and magnolol on the cell viability of colon cancer cells was detected by cell counting kit （CCK-8）. Colony formation assay was used to detect the colony formation capacity of CT2-3 on colon cancer cells. Flow cytometry and Western blot were used to determine the effect of CT2-3 on the apoptosis of colon cancer cells and the expression of DNA damage marker phosphorylated histone H2AX （γH2AX）. Reactive oxygen species （ROS） generation was measured by ROS assay kit. Real time quantitative polymerase chain reaction （Real-time PCR） was used to detect the effect of CT2-3 on expressions of mitochondrial apoptosis-related genes B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X （Bax） in colon cancer cells. Result:The half maximal inhibitory concentration （IC50） of magnolol in two kinds of colon cancer cells after treatment for 24， 48 h were both higher than 80 μmol·L-1. While the IC50 of CT2-3 in SW480 cells after treatment for 24， 48 h were （54.59±1.73） μmol·L-1 and （29.82±1.13） μmol·L-1， respectively. The IC50 of CT2-3 in LoVo cells after treatment for 24，48 h were （66.68±2.11） μmol·L-1 and （46.70±1.81） μmol·L-1， respectively. Compared with the blank group， the colony formation capacity of colon cancer cells in CT2-3 groups （20， 40 μmol·L-1） was significantly decreased in a dose-dependent manner （P<0.01）， apoptotic colon cancer cells were significantly increased （P<0.01）， relative expression of DNA damage marker γH2AX was significantly increased （P<0.01）， ROS was significantly increased （P<0.01）. In addition， relative mRNA expression of Bcl-2 was significantly decreased （P<0.01）， while relative mRNA expression of Bax was significantly increased （P<0.01）. Conclusion:CT2-3 can remarkably inhibit colon cancer cells， and the underlying mechanism might be that CT2-3 promotes mitochondria dysfunction and ROS generation by regulating expressions of mitochondrial apoptosis-related genes， so as to further induce DNA damage and finally lead to apoptosis.