Anticolorectal Cancer Effects of AUCAN: Effects to Suppress Proliferation, Metastasis, and Invasion of Tumor Cells.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is an underlying deadly malignancy with poor prognosis, lacking effective therapies currently available to improve the prognosis. C18H17NO6 (AUCAN), a kind of dibenzofuran extracted from a special plant in Yunnan Province (China), is identified as a natural anticancer agent exerting strong inhibitory activities on various cancers. Our study was committed to investigating the potency of AUCAN against colorectal cancers and further exploring the potential mechanisms via proteomic analysis. METHODS: Cell Counting Kit-8 assay and immunofluorescence staining were used to investigate the effect of AUCAN on the viability and proliferation of HCT-116 cells and RKO cells. The apoptosis of HCT-116 and RKO cells after AUCAN administration was determined by the flow cytometry test. The effects of AUCAN on invasion and migration of tumor cells were investigated by the colony formation assay, wound healing test, and Transwell invasion test. Meanwhile, the energy metabolism and growth of tumor tissues after AUCAN administration with 10 mg/kg and 20 mg/kg were examined by PET-CT in vivo. The side effects of AUCAN treatment were also evaluated through blood routine and liver function examination. RKO cell proliferation and apoptosis in vivo were further determined by hematoxylin and eosin staining, TUNEL staining, and immunohistochemistry. Furthermore, the differentially expressed proteins (DEPs) involved in AUCAN treatment were determined by proteomic analysis followed by functional clustering analysis. RESULTS: The results showed that AUCAN suppressed the migratory abilities and enhanced apoptosis of HCT-116 and RKO cell lines. Meanwhile, AUCAN treatment dramatically depressed the growth and volume of colorectal tumors in nude mice and suppressed the survival of RKO cells in tumor tissues without any side effects on the blood routine and liver function. In addition, twenty-four upregulated and forty-two downregulated proteins were identified. Additionally, functional clustering analysis concealed enriched biological processes, cellular components, molecular functions, and related pathways of these proteins involved in cellular metabolic. Finally, the protein-protein interaction analysis revealed the regulatory connection among these DEPs. CONCLUSIONS: Taken together, AUCAN exerted its significant antitumor effect without side effects in the blood routine and liver function and the underlying mechanisms were preliminarily investigated by proteomic analysis.