Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo.

Te-Chun Hsia,Shu-Fen Peng,Fei-Ting Hsu,Jiun-Long Yang,Kung-Wen Lu,Rick Sai-Chuen Wu,An-Cheng Huang,Fu-Shin Chueh

doi:10.3390/ijms23010538

Abstract

Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.

Highlights

Glioblastoma (GBM) in adults and medulloblastoma and pineoblastoma in children are aggressive brain tumors
GBM 8401/luc2 cells were treated with various concentrations of BDMC for 48 h and cells assayed cell cytotoxicity and apoptosis, and results are shown in Figure 1A,B, which demonstrates that BDMC suppressed total viable cell number and the inhibitory rate was dose-dependently increased following BDMC treatment (p < 0.05)
Treatment dose-dependently increased the cell apoptosis about 3–19 fold; the cell apoptosis was significantly increased after treatment with BDMC compared with the control (p < 0.05)

Summary

Introduction

Glioblastoma (GBM) in adults and medulloblastoma and pineoblastoma in children are aggressive brain tumors. GBM is the fatal form of malignant, lethal primary astrocytic, and a highly angiogenic brain tumor in humans’ central nervous system. The treatment of GBM is still unsatisfied due to its aggressiveness with poor prognosis, with a median survival of 14.6 months from diagnosis [3,4]. Treatments of GBM usually include radiotherapy alongside surgical resection and combined with chemotherapy such as temozolomide (TMZ), which is the landmark treatment protocol [5]. Radiotherapy-induced alterations in the brain microenvironment may result in GBM recurrence and aggressiveness [6]. The survival rate for patients with glioblastoma remains dismal, and around >75%

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