Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells

Abstract

BackgroundMalignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest.MethodsThe anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student’s t-test was used to compare differences between treated groups and their controls.ResultsWe found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice.CoclusionsIn summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.

Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway

“…A far-reaching proposal pointed out that 'given the fact that primary tumors can often be controlled using conventional therapies, could agents that act specifically on the process of metastasis be more likely to increase long term patient survival' [11]. Cancer cell metastasis is related primarily to cell migratory ability and invasiveness.…”

“…Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition [12]. Schisandrin B has been also showed to suppressed glioma proliferation [11]. However, to our present knowledge, it's not clear whether Schisandrin B affects glioma cells migration and invasion.…”

Inhibition of human glioma cell proliferation by altered Bax/Bcl-2-p53 expression and apoptosis induction by Rhaponticum carthamoides extracts from transformed and normal roots

“…The death receptor pathway (extrinsic pathway) and mitochondrial apoptotic pathway (intrinsic pathway) are two major pathways lead to apoptosis . In the death receptor pathway, the binding of ligands to membrane death receptors leads to the activation of caspase‐8 . The mitochondrial apoptotic pathway is regulated by Bcl‐2 family proteins with pro‐ and anti‐apoptotic proteins and characterized by membrane permeability .…”

“…As a result of this change of protein expression levels, the Bax/Bcl‐2 ratios increased approximately two‐ and threefold in the presence of NR and TR extracts, respectively. A high Bax to Bcl‐2 ratio can cause a reduction of mitochondrial membrane potential (ΔΨm) . The loss of mitochondrial membrane potential is an early intracellular event that leads to apoptosis.…”

“…In recent years is a growing interest in medicinal plants due to their bioactive substances. Extracts from plants and their secondary metabolites particularly alkaloids, polyphenolics and terpenoids exhibit anticancer activity by the inhibition of cell proliferation, blocking cell cycle and increasing apoptosis in cancer cells . The plants are inexpensive, easily available and low or absolutely non‐toxic in cancer therapy .…”