Abstract
BackgroundUrsolic acid (UA) is an anti-cancer herbal compound. In the present study, we observed the effects of UA on anchorage-dependent and -independent growth of human colorectal cancer (CRC) RKO cells.MethodsRKO cells were cultured in conventional and detached condition and treated with UA. Cell viability was evaluated by CCK-8 assay. Cell cycle was analyzed by flow cytometry. Apoptosis was identified by Hoechst 33258 staining and flow cytometry analysis. Activities of caspases were measured by commercial kits. Reactive oxygen species (ROS) was recognized by DCFH-DA fluorescent staining. Anoikis was identified by EthD-1 fluorescent staining and flow cytometry analysis. Expression and phosphorylation of proteins were analyzed by western blot.ResultsUA inhibited RKO cell viability in both a dose- and time-dependent manner. UA arrested the cell cycle at the G0/G1 phase, and induced caspase-dependent apoptosis. UA inhibited Bcl-2 expression and increased Bax expression. In addition, UA up-regulated the level of ROS that contributed to UA activated caspase-3, − 8 and − 9, and induced apoptosis. Furthermore, UA inhibited cell growth in a detached condition and induced anoikis in RKO cells that was accompanied by dampened phosphorylation of FAK, PI3K and AKT. UA also inhibited epithelial-mesenchymal transition (EMT) as indicated by the down-regulation of N-Cad expression and up-regulation of E-Cad expression.ConclusionsUA induced caspase-dependent apoptosis, and FAK/PI3K/AKT singling and EMT related anoikis in RKO cells. UA was an effective anti-cancer compound against both anchorage-dependent and -independent growth of RKO cells.
Highlights
Ursolic acid (UA) is an anti-cancer herbal compound
We have demonstrated that Actinidia chinensis Planch (ACP) induces anoikis accompanied by reactive oxygen species (ROS) generation and caspase-3 activation in colorectal cancer (CRC) RKO cells [5]
Scavenger, could counteract UA increased activities of caspase-3, − 8 and − 9, and promoted apoptosis (p < 0.01) (Fig. 6c-f). These results demonstrated that Reactive oxygen species (ROS) participated in the activation of caspases and induction of apoptosis elicited by UA
Summary
Ursolic acid (UA) is an anti-cancer herbal compound. We observed the effects of UA on anchorage-dependent and -independent growth of human colorectal cancer (CRC) RKO cells. Colorectal cancer (CRC) has the third highest malignancies incidence (10.2% of the total cases), and second highest mortality rate (9.2% of the total cancer deaths) globally [1]. CRC can be treated with surgery, chemotherapy and specific targeted therapies. The 5-year survival rate of locally advanced CRC can attain rates as high as 69%; the 5-year survival rate of metastatic CRC is only about 12% [2]. Targeted therapy includes anti-body-mediated therapy against EGFR and VEGF, and small-molecule compounds against protein kinases, such as Regorafenib. The median progression-free survival (mPFS) of metastatic CRC is only 11 months, even when treated by targeted therapy combined with chemotherapy [3].
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