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.

Silibilin-Induces Apoptosis in Breast Cancer Cells by Modulating p53, p21, Bak and Bcl-xl Pathways

“…How silibinin induced cell death and associated signal pathway of apoptosis is not clear. Ghasemiet al showed that silibinin had a strong cytotoxic effect on liver cell line (HepG2 and Hep3B) and caused the cells undergo apoptosis (Ghasemi et al, 2013). In a similar study,silibinin had an inhibitory effect on the growth of MCF-7 cells against UV radiation (Noh et al, 2011).…”

“…Silibinin has introduced with more properties for anticancer application, chemopreventive efficacy and nontoxic roles in humans (Kauntz et al, 2012). General in vitro and in vivo studies demonstrate that the chemoprotective role of silibininaccompanied by cell proliferation, angiogenesis and metastasis in several cancers (Ghasemi et al, 2013). Aim of this study is was to detect that silibinin had a potential inhibitory effect on MCF-7 cells in reducing cell growth and increasing apoptosis.…”

“…Bytheway, flavonoids have been recognized as strong antioxidants which protect cells against oxygen-derived free radicals (Alhazmi et al, 2014). Silibinin is a compound which has been categorized as a subgroup of flavonoligans that constitutes an active portion of the plant extract from milk thistle (scientific name: Silybummarianum) and its anticancer effects have been particularly indicated in hepatocellular carcinoma (Ghasemi et al, 2013). Silibinin is active in enhancing the function of heart, liver detoxification and enhancing its performance, and bronchitis and gall bladder protection (Cecen et al, 2010).…”

Emerging Roles of SPINK1 in Cancer

“…SPINK1 production by hepatocellular cancer cells was increased by lipopolysaccharide, suggesting a role as an acute-phase reactant in HCC (46 ). A more recent study using HepG2 and PLC cells showed that a liver-protective drug, silibilin, reduced SPINK1 expression together with a panel of other genes linked to HCC tumorigenesis (47 ). These results suggest that SPINK1 is a potential target for cancer therapy.…”

Silibinin, up-regulates chemokine receptor expression in MDA-MB-231 breast cancer cell line

“…However, in a study by Ghasemi et al it is suggested that silibininis able to suppress the transcriptional levels of CCR7 in HepG-2 and PLC/PRF/5 hepatoma cells 21 . Inour study to investigate the effect of various concentrations of silibinin(0, 50, 75 and 100 μM) on CXCR3, CCR5 and CCR7 genes expression on MDA-MB-231 cell lines after 24, 48 and 72 h, Real-Time PCR was used.…”