TKP, a serine protease extracted from Trichosanthes kirilowii, inhibits the migration and invasion of colorectal adenocarcinoma cells by targeting Wnt/β‐catenin and Hedgehog/Gli1 signalings

• DOI: 10.1002/ptr.6569
• Publication Date: 2019-12-19T06:01:25Z
• Authors: Xiaomei Sun; Xiaobo Xu; Li Song
• Keywords: 0303 health sciences; Plant Extracts; Trichosanthes; Adenocarcinoma; HCT116 Cells; Antineoplastic Agents, Phytogenic; Zinc Finger Protein GLI1; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; Hedgehog Proteins; Neoplasm Invasiveness; Serine Proteases; Colorectal Neoplasms; Wnt Signaling Pathway; beta Catenin; Cell Proliferation; Signal Transduction

Trichosanthes kirilowii, which is a type of Liana from cucurbitaceous family, possesses many bioactive constituents and therefore has multifarious pharmacological functions. TKP, which is a serine protease extracted from the fruit of Trichosanthes kirilowii, has been reported to possess potential anticancer activity. However, the effects of TKP on cancer cell migration and invasion are still unknown. Here, we reported that TKP could inhibit the migration and invasion abilities of colorectal cancer cells. In addition, the mRNA, protein expression levels, and activities of migration and invasion‐related proteins MMP2 and MMP9 were decreased in TKP‐treated cells. Mechanistically, TKP treatment repressed Wnt/β‐catenin and Hedgehog/Gli1 signaling cascades. However, the addition of lithium chloride or the transfection of plasmid pcDNA3.1‐V5‐HisA‐Gli1 reversed the impacts of TKP on MMP2, MMP9, cell migration, and invasion. These results indicated that TKP suppressed the migration and invasion of colorectal cancer cells through blocking Wnt/β‐catenin and Hedgehog/Gli1 pathways‐mediated MMP2 and MMP9.