Cucurbitacin B Inhibits the Hippo-YAP Signaling Pathway and Exerts Anticancer Activity in Colorectal Cancer Cells
Yanting Chai, Ke Xiang, Yezi Wu, Te Zhang, Ying Liu, Xuewen Liu, Weiguo Zhen, Yuan Si
Child Health Center, Shiyan Maternal and Child Health Hospital, Shiyan, Hubei, China (mainland)
Med Sci Monit 2018; 24:9251-9258
Colorectal carcinoma (CRC) is one of the most frequently diagnosed malignancies. Cucurbitacin B (CuB) is a natural compound isolated from herbs and shows anticancer activity in several cancers.
MATERIAL AND METHODS: Here, we analyzed the eï¬€ects of diï¬€erent CuB concentrations on the proliferative and invasive behaviors of CRC cells using MTT, clonogenic assay, Transwell invasion, and wound healing assays. Flow cytometry was performed to measure the apoptotic eï¬€ects of CuB on CRC cells. Western blot and real-time PCR were used to investigate the expression of apoptosis and Hippo-YAP signaling pathway proteins.
RESULTS: CuB inhibited the proliferation and invasion of CRC cells while promoting apoptosis. In addition, the Western blot and real-time PCR results indicated that CuB suppressed YAP expression and its downstream target genes Cyr 61 and c-Myc in CRC cells. To assess the underlying mechanism, we investigated the upstream regulating factor LATS1, and the results revealed that CuB upregulated LATS1 expression in CRC cells.
CONCLUSIONS: In conclusion, our findings uncovered a novel therapeutic mechanism of CuB and suggest that there is therapeutic potential and feasibility in developing novel YAP inhibitors for cancer treatment.
Keywords: Colonic Neoplasms, Medicine, Chinese Traditional, Neoplasm Invasiveness, Signal Transduction