Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo

• DOI: 10.1038/srep12889
• Publication Date: 2015-08-06T09:06:47Z
• Authors: Xing Yuan; Hao Chen; Xia Li; Ming Dai; Huawu Zeng; Lei Shan; Qingyan Sun; Weidong Zhang
• Keywords: Male; Mice, Inbred BALB C; 0303 health sciences; Carcinoma, Hepatocellular; Liver Neoplasms; Mice, Nude; Apoptosis; Hep G2 Cells; Xenograft Model Antitumor Assays; Article; Neoplasm Proteins; Mice; 03 medical and health sciences; Xanthenes; Animals; Humans; Neoplasm Metastasis; Protein Kinase C

Abstract Targeted inhibition of protein kinase C (PKC) inhibits hepatocellular carcinoma (HCC) proliferation and metastasis. We previously reported the cytotoxicity a series synthetic phenyl-substituted polyoxygenated xanthone derivatives against human HCC. In current study, most potent natural product, isojacareubin (ISJ), was synthesized its cellular-level antihepatoma activities were evaluated. ISJ significantly inhibited cell highly selective for HCC cells in comparison to nonmalignant QSG-7701 hepatocytes. Moreover, exhibited pro-apoptotic effects on HepG2 hepatoma cells, as well impaired migration invasion. Furthermore, inhibitor PKC, with differential actions various PKC isotypes. selectively expression aPKC (PKCζ) cytosol translocation cytosolic PKCζ membrane site. also directly interacted cPKC (PKCα) nPKC (PKCδ, PKCε PKCμ) thereby early response major MAPK phosphorylation late invasion proliferation. xenograft model, pretreatment resulted significant activity vivo . These findings identify promising lead compound development new agents may guide search additional inhibitors.