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Background: Colorectal cancer, as a general malignancy of the digestive system, has long constituted a threat to the health of the population and the development of the social economy. It has been widely recognized that exploiting a drug with weaken toxic side effects and excellent antitumor activity can be a viable and promising strategy. Nitidine chloride is a typical bioactive base extracted from the dried roots of the Zanthoxylum nitidum (Roxb.) DC, has been clinically evidenced to exhibit robust immune efficacy against several types of tumor cells. However, the underlying function mechanism of the anti-colorectal-cancer effectiveness is still in its exploratory stage and thereby deserves further in-depth investigations.Objective: To examine the anti-cancer activity of Nitidine chloride against colorectal cancer in vitro and in vivo and its mechanism of effect.Methods: In this work, we combined a series of cellular characterization techniques to examine the inhibitory effect of Nitidine chloride (NC) on colorectal cancer cells, including RKO, HCT116 and HT29 cells. In addition, the potential signaling pathways were clarified via transcriptome sequencing technique. Moreover, we proposed a reliable biomedical mechanism towards the inhibition effects of the NC against colorectal cancer on the basis of qRT-PCR and western blot.Results: At first, we examined the toxic effect of NC on several colorectal cancer cells (RKO, HCT116 and HT29), within which the value of IC30 and IC50 were determined to be 2 µM and 3 µM for RKO; 3.5 µM and 5 µM for HCT116; and 6 µM and 10 µM for HT29, respectively. Through transcriptome sequencing, it is acquired that the p53 pathway and downstream signaling was prominently activated, indicating that NC is strongly correlated with cell proliferation and apoptosis. We also reveal that NC was able to suppress malignant behaviors, including proliferation, migration, invasion and tumor formation in RKO, HCT116 and HT29 cells. Besides, NC treatment significantly modified EMT-related hall marker proteins, including E-cadherin, N-cadherin and MMP9, which is indicative of the inhibition of EMT. Furthermore, the IC50 of NC significantly upregulated the pro-apoptosis-related factors, including Bax, Noxa, and caspase-3 and down-regulated the apoptosis-inhibiting factor Bcl2. Conclusion: In conclusion, the above experimental results and data analysis pointed out that colorectal cancer can be considerably suppressed by NC treatment, which effectively activates p53 signaling. Our approach should hold substantial promise for therapeutic applications in the therapy of colorectal cancer. |
