Silybin-Induced Apoptosis Occurs in Parallel to the Increase of Ceramides Synthesis and miRNAs Secretion in Human Hepatocarcinoma Cells

Abstract

Silybin is a flavonolignan extracted from Silybum marianum (milk thistle) with hepatoprotective, antioxidant, and anti-inflammatory activity. Several studies have shown that silybin is highly effective to prevent and treat different types of cancer and that its antitumor mechanisms involve the arrest of the cell cycle and/or apoptosis. An MTT assay was performed to study cell viability, lipid peroxidation, extracellular NO production, and scavenger enzyme activity were studied by Thiobarbituric Acid-Reactive Species (TBARS) assay, NO assay, and MnSOD assay, respectively. Cell cycle and apoptosis analysis were performed by FACS. miRNA profiling were evaluated by real time PCR. In this study, we demonstrated that Silybin induced growth inhibition blocking the Hepg2 cells in G1 phase of cell cycle and activating the process of programmed cell death. Moreover, the antiproliferative effects of silybin were paralleled by a strong increase of the number of ceramides involved in the modulation of miRNA secretion. In particular, after treatment with silybin, miR223-3p and miR16-5p were upregulated, while miR-92-3p was downregulated (p < 0.05). In conclusion, our results suggest that silybin-Induced apoptosis occurs in parallel to the increase of ceramides synthesis and miRNAs secretion in HepG2 cells.

Anticancer Potential of Silibinin Loaded Polymeric Nanoparticles against Breast Cancer Cells: Insight into the Apoptotic Genes Targets

“…Previous studies found that SIL inhibits ERK1/2 signaling, which indicates that the ERK1/2 signaling pathway may play as an upstream regulator that modulates the SIL-induced Bim signaling pathway. In addition, the effect of SIL on the prohibition of angiogenesis in hepatic cancers is associated with reduced secretion of vascular endothelial growth factor, CD34, and metalloproteinase-2 in a dose dependent manner (Li and Wang, 2016;Zappavigna et al, 2019).…”

Tackling of Renal Carcinogenesis in Wistar Rats by Silybum marianum Total Extract, Silymarin, and Silibinin via Modulation of Oxidative Stress, Apoptosis, Nrf2, PPARγ, NF‐κB, and PI3K/Akt Signaling Pathways

“…Silymarin (Sm) and silibinin (Sb) are investigated to exert strong antineoplastic effects in both in vitro and in vivo models of cancer, including cancers of the prostate, bladder, skin, colon, lung, breast, and kidney [35][36][37][38][39][40][41]. During Sm and Sb treatment, several mechanisms have been applied, such as DNA repair, cell cycle arrest, inhibition of growth and pro-liferation in addition to antiangiogenic effects, and blockage of invasion and metastasis [42,43].…”

Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis

“…Studies have proved that the abnormal expression of miRs is related to the development of a series of cancers, including HCC [ 29 , 30 ]. Also, circRNAs take part in the advancement of a range of tumors by sponging miRs [ 31 ].…”