Effects of terpinene-4-ol on malignant behavior of colorectal cancer cells and its mechanism / 中国药理学通报

ABSTRACT

Aim To investigate the effect of terpinene 4-alcohol(T4O)on the malignant behavior of colorectal cancer cell RKO and HCT116 and the underlying mechanism. Methods RKO and HCT116 cells were treated with 0, 1, 2, 4 μmol·L-1 T4O and 4 μmol·L-1 5-Fu, respectively. The proliferation, clonal formation, apoptosis, cell cycle, migration and invasion of RKO and HCT116 cells were detected by CCK-8, colony formation, flow cytometry, wound healing and Transwell assay; the expressions of E-Cadherin, N-Cadherin, p21, CyclinB1 and cleaved-Caspase7 in each group of cells were detected by Western blot. Based on pharmacophore, the target of T4O was analyzed and then the effects of T4O on the expression and degradation rate of NR3C1 were explored. NR3C1 knockdown cells were constructed, and the effects of NR3C1 knockdown on the proliferating and migrating inhibition induced by T4O were detected by wound healing and CCK-8 assay. Results T4O significantly inhibited the proliferation, colony formation, migration and invasion of RKO and HCT116 cells, as well as induced apoptosis and G1 phase arrest(P all <0. 05). The effect of T4O was better than that induced by 5-Fu with the same dose. T4O obviously reduced N-Cadherin and Cyclin B1 expression, and elevated the E-Cadherin, p21 and cleaved-Caspase7 expression(P all <0. 05). A total of 10 targets of T4O were discovered, among which NR3C1 had the highest binding score. After T4O treatment, NR3C1 level in cells increased obviously, and the degradation rate decreased markedly(P<0.05). NRC3C1 knockdown significantly relieved the inhibitory effects of T4O on cell prolfieration and migration(P<0.05). Conclusion T4O can inhibit the malignant behavior of colorectal cancer cells RKO and HCT116 by maintaining the stability of NR3C1 protein.