Abstract：
AIMS:Dysfunction of the Hippo-Yes-Associated Protein (YAP) signaling pathway is known to be associated with hepatocellular carcinoma (HCC). Evodiamine (Evo), a plant-derived bioactive alkaloid, exerts inhibitory effects on cancer. However, the precise influence of Evo on HCC and its potential effects on Hippo-YAP signaling have yet to be ascertained. Here, the effects of Evo on cell proliferation and apoptosis were evaluated using HCC cell lines (HepG2 and Bel-7402) and nude mice with xenograft tumors. We further investigated whether Evo exerts anti-HCC activity through effects on Hippo-YAP signaling in vitro with the aid of XMU-MP-1, an inhibitor of the key component of this pathway, mammalian sterile 20-like kinase 1/2. MAIN METHODS:Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine staining, colony formation, flow cytometry, hematoxylin-eosin and dUTP nick-end labeling experiments. Bioinformatics and real-time quantitative polymerase chain reaction (RT-qPCR) arrays were performed to determine the associations among Evo, HCC progression and the Hippo-YAP pathway. The expression patterns of components of Hippo-YAP signaling and apoptotic genes were further examined via RT-qPCR and immunoblotting. KEY FINDINGS:Evo inhibited proliferation and promoted apoptosis of HCC cell lines in vitro, and attenuated xenograft tumor formation in nude mice in vivo. Mechanistically, Evo treatment stimulated the Hippo-YAP signaling pathway. In vitro, the effects of Evo on HCC cell proliferation and apoptosis were alleviated by XMU-MP-1. SIGNIFICANCE:Our collective results revealed that the anti-HCC effects of Evo were correlated with the Hippo-YAP signaling pathway.
journal_name
Life Scijournal_title
Life sciencesauthors
Zhao S,Xu K,Jiang R,Li DY,Guo XX,Zhou P,Tang JF,Li LS,Zeng D,Hu L,Ran JH,Li J,Chen DLdoi
10.1016/j.lfs.2020.117424subject
Has Abstractpub_date
2020-06-15 00:00:00pages
117424eissn
0024-3205issn
1879-0631pii
S0024-3205(20)30171-5journal_volume
251pub_type
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