Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1

• DOI: 10.1038/s41419-020-2227-4
• Publication Date: 2020-01-24T09:03:03Z
• Authors: Hai Zhang; Yu-ping Tan; Lin Zhao; Lun Wang; Nai-jie Fu; Song-ping Zheng; Xiao-fei Shen
• Keywords: Xanthone; Garcinia Mangostana; Hepatic carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide. The dietary xanthone α-mangostin (α-MGT) exhibits potent anti-tumor effects in vitro and vivo. However, anti-HCC α-MGT their underlying mechanisms are still vague. Aberrant activation signal transducer activator transcription 3 (STAT3) involved progression HCC. We therefore investigated whether inhibited STAT3 thereby its effects. In this study, we found that significantly suppressed cell proliferation, induced cycle arrest, triggered apoptosis HCC cells, including HepG2, SK-Hep-1, Huh7, SMMC-7721 cells vitro, as well inhibiting tumor growth nude mice bearing HepG2 or SK-Hep-1 xenografts. Furthermore, potently constitutive inducible cells. addition, also IL-6-induced dimerization nuclear translocation STAT3, which led to inhibition expression STAT3-regulated genes at both mRNA protein levels. Mechanistically, exhibited effective STAT3's upstream kinases, JAK2, Src, ERK, Akt. Importantly, increased level Src homology region 2 domain-containing phosphatase-1 (SHP1), a key negative regulator signaling pathway. enhanced stabilization SHP1 by degradation mediated ubiquitin-proteasome Knockdown using siRNA obviously prevented α-MGT-mediated proliferation summary, effect blocking pathway via suppression These findings suggested potential derived therapy.