title: Hydroxysafflor yellow A inhibits angiogenesis of hepatocellular carcinoma via blocking ERK/MAPK and NF-κB signaling pathway in H22 tumor-bearing mice.
abstract: Hydroxysafflor yellow A (HSYA), a flavonoid derived and isolated from traditional Chinese medicine Carthamus tinctorius L., possesses anti-tumor activity. However, its effects on hepatocellular carcinoma (HCC) have not been investigated. The proliferation and metastasis of HCC are dependent on angiogenesis, which also strongly links with several signal transduction pathways associated with cell proliferation and apoptosis. This study aimed to explore the effect of HSYA on vasculogenesis and to determine its molecular mechanism by investigating the expression of ERK/MAPK (p-c-Raf, c-Raf, p-ERK1/2, ERK1/2) and NF-κB (p65, IκB and p-IκB) signaling pathway in H22 tumor-bearing mice. The results showed that HSYA could considerably suppress tumor growth by inhibiting secretion of angiogenesis factors (vascular endothelial growth factor A, basic fibroblast growth factor) and vascular endothelial growth factor receptor1. At the moleculcould block ERK1/2 phosphorylation and then restrain the activation of NF-κB and its nuclear translocation by down-regulating the expression of p65 in the nucleus, up-regulating p65 level in the cytoplasm, inhibiting IκB phosphorylation and cytoplasmic degradation of IκB-α. Finally, we demonstrate that HSYA could suppress mRNA expression levels of cell proliferation-related genes (cyclinD1, c-myc, c-Fos) compared with negative control group. And best of all, HSYA could improve spleen/thymus indexes, which was evaluated as the marker of protective effect on the immune system. Our findings support HSYA as a promising candidate for the prevention and treatment of HCC.
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, PR China; Department of Medical Oncology, Affiliated Hospital of Binzhou Medical College, Binzhou 256600, Shandong, PR China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, PR China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Li
authors.affiliation: Wang Ge Zhuang Central Hospital, Qingdao 266000, Shandong, PR China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Binzhou Medical College, Binzhou 256600, Shandong, PR China. Electronic address: byfychenss@126.com.
authors.forename: Shaoshui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Binzhou Medical University, Yantai, Shandong 264003, PR China. Electronic address: xybai1963@126.com.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Bai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011809:Quinones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016328:NF-kappa B; D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone
keywords: Hepatocellular carcinoma; Hydroxysafflor yellow A; Hydroxysafflor yellow A (PubChem CID: 6443665); NF-κB signaling pathway; Ras/Raf/Mek/Erk pathway; Sodium deoxycholate (PubChem CID: 23668196); Sodium dodecyl sulfate (PubChem CID: 3423265); Sorafenib (PubChem CID: 216239); Tris (PubChem CID: 6503); Triton X­100(PubChem CID: 5590)