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Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL-60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose- and time-dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 μM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT-22 cells, with an IC50 value of 6.24 μM. Cell apoptosis was assessed by flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6-induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase-3, -8 and -9, and decreases in the levels of B-cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM. [ABSTRACT FROM AUTHOR]

The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood-brain-tumor barrier. In the present study, cyclic Arginine-Glycine-Aspartic acid-D-Tyrosine-Lysine [c(RGDyK)], that has a high binding affinity to integrin avβ3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid-polyethylene glycol (DTX-PLA-PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine-Glycine-Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX-PLA-PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non-targeted micelles showed limited transport ability. Furthermore, RGD-linked micelles showed marked anti-glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand-mediated drug delivery may improve the efficacy of brain cancer chemotherapy. [ABSTRACT FROM AUTHOR]