Silibinin Inhibits Glioblastoma Cell Proliferation via Akt/S6/4EBP1 and Stat3 Signaling Pathways In Vitro

Abstract

Glioblastoma is the most common primary and lethal brain tumor in humans. These malignant astrocytic tumors exhibit high proliferation rates and acquire resistance against many therapeutic regimens. Despite aggressive treatment including surgery, radiation, and chemotherapy, the median survival time of 12‐15 months after diagnosis has remained unchanged.Thus, new effective strategies for controlling glioblastoma are required. Because glioblastoma cells like any cancer cells avoid differentiation and apoptosis, the induction of differentiation and apoptosis in glioblastoma cells may be considered as a potential treatment strategy. Silibinin, a natural polyphenolic flavonoid, is a major bioactive component of silymarin, which is isolated from the plant milk thistle. Recent studies have indicated that silibinin has anticancer activities in various cancers including prostate cancer in both in vitro and in vivo models. The present study investigated the effect of silibinin on glioblastoma cell proliferation in vitro. U87MG cells were grown on well tissue culture plates and cell viability was measured by MTT assay. The expression and activity of AKT, S6K, 4EBP1, and STAT3 proteins were measured by Western blot analysis. Silibinin induced cell death as well as inhibited proliferation in a dose‐ and time‐dependent manner. Accordingly, levels of biologically active phospho‐AKT, phospho‐S6K, phospho‐4EBP1 and phospho‐STAT3 were decreased in a dose‐ and time‐dependent manner. This study demonstrates that silibinin bears an anti‐oncogenic property via inhibition of PI3K/Akt and STAT pathways against GBM cells in vitro. Thus, this study promises a great potential agent for Glioblastoma. Study supported by the science research funds of AMS College of Pharmacy, LIU, NY