title: Multitargeting and antimetastatic potentials of silibinin in human HepG-2 and PLC/PRF/5 hepatoma cells.
abstract: Hepatocellular carcinoma (HCC) is the most common sort of primary liver malignancy with poor prognosis. This study aimed at examining the effects of silibinin (a putative antimetastatic agent) on some transcriptional markers mechanistically related to HCC recurrence and metastasis in HepG-2 [hepatitis B virus (HBV)-negative and P53 intact) and PLC/PRF/5 (HBV-positive and P53 mutated) cells. The expression of 27 genes in response to silibinin was evaluated by real-time RT-PCR. The MMP gelatinolytic assay and microculture tetrazolium test (MTT) were tested. Silibinin was capable of suppressing the transcriptional levels of ANGPT2, ATP6L, CAP2, CCR6, CCR7, CLDN-10, cortactin, CXCR4, GLI2, HK2, ID1, KIAA0101, mortalin, PAK1, RHOA, SPINK1, and STMN1 as well as the enzymatic activity of MMP-2 but promoted the transcripts of CREB3L3, DDX3X, and PROX1 in both cells. Some significant differences between the cells in response to silibinin were detected that might be related to the differences of the cells in terms of HBV infection and/or P53 mutation, suggesting the possible influence of silibinin on HCC through biological functions of these 2 prognostic factors. In conclusion, our findings suggest that silibinin could potentially function as a multitargeting antimetastatic agent and might provide new insights for HCC therapy particularly for HBV-related and/or P53-mutated HCCs.
authors: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Reza
authors: R
authors: Ghasemi
authors: Seyed H
authors: SH
authors: Ghaffari
authors: Majid
authors: M
authors: Momeny
authors: Saeed
authors: S
authors: Pirouzpanah
authors: Mehdi
authors: M
authors: Yousefi
authors: Mohsen
authors: M
authors: Malehmir
authors: Kamran
authors: K
authors: Alimoghaddam
authors: Ardeshir
authors: A
authors: Ghavamzadeh
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53; D056945:Hep G2 Cells / Q000187:drug effects; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009154:Mutation; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012838:Silymarin; D000077385:Silybin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9